VETERINARY PEPTIDES Peptides in Veterinary Medicine
PEPTIDES IN VETERINARY MEDICINE
Bachem offers a choice of generic peptides for use as active ingredients in veterinary medicine, amongst them gonadorelin and gonadorelin agonists and antagonists. For a compilation of our peptide APIs please see page 20. Our offer is comple- mented by the corresponding peptides in research quality to be found on page 23-25. Additionally, we provide the anesthetics etomidate and pro- pofol as non-peptide generic APIs for the veterinary practice, please see page 21.
Introduction Peptide-based drugs are especially indicated for treating animals used in A considerable number of peptides applied food production, as they are highly active as therapeutics or diagnostics in humans is compounds which require only very small also used for various indications in veteri- doses. Additionally, they are metabolized nary medicine. more readily than organic compounds, Peptides are relatively expensive drugs which reduces the risk of contamination of which, in most cases, can’t be applied orally, the milk, eggs, or meat of the treated animal but these shortcomings are often out- by the unmetabolized pharmaceutical and/ weighed by their advantages. or its degradation products. There is also a vast market for peptide drugs in the treatment of companion ani- mals and horses. Pets can suffer from most diseases of civilization that affect humans. Accordingly, diabetes has become a grow- ing problem with dogs and cats in recent years due to their increasing life expectancy PEPTIDE in combination with obesity and lack of exercise. At the same time, owners are more THERAPEUTICS willing to pay for medication and therapies to increase the length and quality of life of Administration of synthetic peptides their diseased pets. This also holds true for as therapeutics or diagnostics is companion animals suffering from cancer well-established in human medicine. and other life-threatening diseases. A few of them have also found use for Synthetic peptides have also gained impor- comparable indications in veterinary tance as diagnostics, especially in the case medicine. of small animals, which creates a further growing market for these compounds. Nevertheless, reproduction management
2 is the most important and best established for the use of much lower doses and thus In addition to our offer area of usage for peptide drugs in veterinary reduces treatment costs. For example, the of peptide generic APIs medicine and animal husbandry. Synthetic activity of buserelin was shown to be 100 to we provide research- grade analogs, frag- peptide hormones and analogs are em- 200 times higher than the activity of GnRH, ments and Ph. Eur. ployed to stimulate and facilitate breeding and fertirelin was 2.5 to 10 times more impurities for quality as well as to prevent unwanted offspring. active than the natural peptide. In female control. Please visit our Livestock as well as companion animals dogs, a single dose of buserelin during heat online shop at are treated with LHRH (GnRH, gonadorelin) will induce ovulation. In cows, a postin- shop.bachem.com and its agonists and antagonists to regulate seminal application will assist the corpus fertility and reproduction as well as to treat luteum, and administration coinciding with disorders of the reproductive tract. insemination will delay ovulation, which al- A number of LHRH analogs have been ap- ternatively can be induced by an injection of plied in the regulation of reproduction in fertirelin 10 to 17 days postpartum. Repeti- animals: tive injections of buserelin in mares will ef- fect the onset of heat or ovulation, whereas
Alarelin in rabbits, a single injection of a GnRH Azagly-Nafarelin analog induces ovulation and increases the Buserelin conception rate. Buserelin and fertirelin Deslorelin have also been used in ewes. Overdosage Fertirelin of these highly active peptides can have a detrimental effect on ovarian response. Goserelin Deslorelin is administered as an injection Lecirelin or implant to induce a reversible infertility Leuprolide in pets, especially in males. These implants Lutrelin can postpone the estrus of bitches for more Nafarelin than 2 years and have found use in the re- Peforelin production management of extensive cattle Triptorelin farming. Long-term release formulations of leuprolide have been shown to postpone puberty and reversibly suppressed repro- ductive function in male and female dogs Gonadotropin-Releasing Hormone for periods exceeding 1 year. (GnRH, LHRH) and Analogs Peforelin, which is used in the reproduction management of swine, is a naturally occur- Besides GnRH, deslorelin, leuprolide, and ring peptide and corresponds to lamprey buserelin are probably the most often LHRH III. Peforelin is applied to induce the commonly prescribed synthetic peptides in estrus of the sow after weaning. Depot veterinary medicine and livestock breeding. formulations of triptorelin have been tested GnRH agonists are metabolized more slowly in heifers and gilts. than the native hormone which allows
THERE IS A VAST MARKET FOR PEPTIDE DRUGS IN THE TREATMENT OF COMPANION ANIMALS AND HORSES
3 Peptides in Veterinary Medicine
GnRH agonists such as deslorelin and by timed artificial insemination in the next leuprolide are applied as implants for long- 8 to 24 hours. The efficiency of the syn- term reproduction management not only in chronization in lactating dairy cows can domestic animals. Implants facilitate long- be further improved by pretreatment with
term administration and allow non-surgical an additional dose of PGF2α (8 days before sterilization of stray dogs and cats, popula- starting Ovsynch) and GnRH (6 days before tion control in wildlife, and reproduction starting Ovsynch) (“G6G”, Bello et al., 2006). management in zoos. Unfortunately, heifers respond only poorly In dairy cattle and camelids, GnRH and to Ovsynch and artificial insemination, but GnRH analogs such as buserelin or fertirelin suitable modifications of the protocol could are indicated for the treatment of ovarian be developed. cysts. Deslorelin is commonly applied as Buserelin, fertirelin and other GnRH ago- an implant for treating hyperadrenocorti- nists have also been administered in syn- cism in domestic ferrets. Gonadorelin can chronization schemes. For example, in the also be used as a diagnostic in disorders of recently described Doublesynch scheme, the reproductive system, e.g. in dogs with lecirelin has been shown to be especially hypogonadotropic hypogonadism to differ- suitable for primiparous cows. entiate between pituitary and hypothalamic defects. GnRH in aquaculture Not all fish species can be bred efficiently Anti-GnRH vaccines by stimulating reproduction with GnRH ago- As an additional tool for non-surgical nists. Hence, the development of combina- spaying, anti-GnRH vaccines were recently tion products composed of GnRH agonists developed. The C-terminally elongated as (Des-Gly10, D-Arg6, Pro-NHEt9)-salmon peptide hormone is linked to a carrier GnRH (sGnRH-A), or alarelin (LHRH-A), and protein, and the resulting conjugate is ap- dopamine D2 receptor antagonists as pimo- plied in combination with an adjuvant to zine or domperidone meant a breakthrough achieve immunization against endogenous for fish farming, as they allowed reliable LHRH. A GnRH-keyhole limpet hemocyanin induction and synchronization of ovula- conjugate vaccine has been developed as tion and spawning („Linpe method“). The a contraceptive to control wildlife. Effec- synthetic stimulators yield spawn of much tive after a single vaccination, it has been higher quality than the pituitary extracts applied to bison, deer, feral pigs, and others. used in controlled fish reproduction. The In male pigs, the anti-LHRH-vaccine is dopamine antagonist inhibits the synthesis injected in two doses several weeks before of gonadotropin. The mixture of the ingredi- slaughtering to control boar taint. Another ents is applied as single dose injection or in anti-LHRH-vaccine has been registered for pelleted form. The pellets serve as short- the treatment of benign prostatic hyperpla- term controlled release implants. Injectable sia in dogs. drugs containing a combination of sGnRH- A and domperidone are employed in the Ovsynch controlled hatching of salmon, trout and The synchronization of ovulation in dairy many other cultured marine and freshwater cattle is the most important application of fish species, as well as in the breeding of GnRH and analogs in animal husbandry. ornamental fish. The combination of the The Ovsynch protocol using gonadorelin dopamine antagonist metoclopramide and for the controlled induction of ovulation LHRH-A in pelleted form assists e.g. in the was developed in 1995 by R. Pursley and culturing of freshwater fish as carp, chub N. Bello at Michigan State University. The and catfish species. program consists of an initial injection of GnRH followed 7 days later by an injec- GnRH antagonists
tion of prostaglandin F2α(PGF2α). It can be Whereas the veterinarian can choose from started at any stage of the estrous cycle. a number of proven, highly active and ef-
Two days following the PGF2α injection, cows ficient GnRH agonists, the situation on receive a second GnRH injection followed the antagonist side is not yet satisfactory.
4 Third-generation antagonists such as acyl- analog is secreted in pigs. The porcine Peptide-based drugs ine, antarelix, antide (iturelix), and cetrorelix analog shows only half of the antidiuretic are especially indicated have been used in studies with domestic activity of AVP. In higher dosage, vasopres- for treating animals used in food produc- animals, e.g. to prevent ovulation during sin additionally induces vasoconstriction tion, though regulation proestrus or terminate pregnancy. and stimulates the production of factor VIII of fertility is their most and von Willebrand factor. important application. Vasopressin is administered intravenously Only very small doses of Oxytocin and Carbetoxin or subcutaneously as a diagnostic to differ- these rather expensive, entiate between renal and central diabetes but highly active com- Oxytocin and its more stable carba ana- insipidus in dogs, cats, horses, and cattle. pounds are required. Peptides are metabo- log carbetocin are administered to induce AVP can also be used as a therapeutic in lized more readily than normal labor and facilitate parturition in the treatment of the central form of the many small molecules, livestock (cows, ewes, sows, goats) as well disease. However, due to its short half-life, which reduces the risk as in pets. In captive birds such as budgeri- its stable synthetic analog desmopres- of contamination of the gars or cockatiels, oxytocin and its avian sin (DDAVP) is the preferred medication in milk, eggs, or meat of analog vasotocin help to induce oviposition the treatment of dogs and cats suffering the treated animal. in case of egg binding. from polyurea caused by diabetes insipi- Oxytocin, which is produced in the hypo- dus centralis. Compared to vasopressin, thalamus, and synthetic carbetocin act desmopressin shows an improved an- on the smooth musculature of the female tidiuretic and a reduced vasoconstrictive reproductive system. Both peptides induce activity, it more effectively stimulates factor strong contractions of the estrogen- VIII and von Willebrand factor production. stimulated uterus, but distinctly prolonged DDAVP is often applied conjunctivally or and more frequent contractions will result nasally in dogs and cats, and has even been during administration of the analog. Si- administered orally in humans. It is applied multaneously, these hormones stimulate intravenously or subcutaneously in dogs for the lactating glands to produce milk and treating moderate cases of von Willebrand’s deblock the teats for ejection. disease before surgery to avoid hemor- Oxytocin and carbetocin are also applied in rhagia. In animals with von Willebrand’s case of agalactia or reduced milk flow after disease, desmopressin transiently elevates birth. In cows, carbetocin is administered to von Willebrand’s factor and shortens bleed- prevent a retarded involution of the uterus ing time. It may be useful in dogs with von or in case of abnormal milk ejection. A Willebrand’s disease permitting surgical single injection of carbetocin in dysgalactic procedures or controlling capillary bleeding. sows induces milk flow post partum. The hemostatic effect in cats has not yet If drug overdosage may cause problems been evaluated. oxytocin is preferred over carbetocin due to Vasopressin is gaining attention in veteri- its shorter half-life. nary emergency medicine as a cardiovas- In large animals, oxytocin is administered cular resuscitation drug in small animal to stimulate the expulsion of placenta after patients and newborn foals. parturition in case of prolonged retention. Oxytocin is also applied therapeutically: in mares, it is indicated for the treatment Glucagon, Peptides in Pancreatic of endometritis following insemination. In Disorders cows and swine, it is used to treat mastitis. Glucagon Glucagon, as its antagonist insulin, is Vasopressin and Desmopressin secreted by the pancreas. The peptide hor- mone is used as emergency medication in Vasopressin (Antidiuretic Hormone, ADH), cases of severe hypoglycemia, as it upregu- a peptide hormone secreted by the hypo- lates plasma glucose. thalamus, acts on the renal tubulus cells. Management of bovine fatty liver disease Most mammals produce (Arg8)-Vasopressin (FLD, Steatosis hepatis) is an important (Arg-Vasopressin, AVP), whereas the Lys8- application of this hormone in veterinary
5 Peptides in Veterinary Medicine
medicine. FLD is an accumulation of fat (es- half-life, was evaluated in the manage- pecially triglycerides) in the liver occurring ment of insulinomas in dogs. in cows after calving. The disease can be Octreotide is a long-acting inhibitor of pan- treated efficiently by longterm intravenous creatic secretion, which helps to prevent infusion of glucagon. Besides stimulat- complications after pancreatic surgery. ing glycogenolysis, gluconeogenesis, and Single photon emission computed tomog- insulin production, the peptide hormone raphy (SPECT) applying 111In-pentetreotide reduces liver triglycerides. Glucagon is also allows the detection and localization of used as a diagnostic in veterinary medi- canine insulinomas. cine, especially in dogs (Glucagon stimula- tion test). Diagnostics Intravenously injected glucagon causes a short rise in the plasma concentration TRH of insulin in healthy dogs. This will not As in humans, protirelin (TRH) is injected or happen when administrating glucagon to infused in pet dogs for diagnosing thyroid diabetic canines due to their inability to disorders as hypothyroidism. TRH acts on produce the hormone. But instead of mea- the anterior pituitary gland. In the case suring the secreted insulin, determination of a healthy pituitary, application of the of the amount of the concomitantly formed hormone stimulates the secretion of TSH, C-peptide is preferred, as it is not affected which promotes the secretion of triiodo- by insulin treatment. The measurement is thyronine (T3) and thyroxin (T4) from the performed 10 minutes after the glucagon thyroid gland. T3 and T4 can be measured injection. in plasma later on. In horses, a TRH test alone or in combina- C-Peptide tion with the dexamethasone suppres- Canine C-peptide is applied as a diagnos- sion test (DST) is performed to diagnose tic tool for monitoring diabetes in dogs. pituitary gland hyperplasia (pituitary pars This peptide is released together with intermedia dysfunction (PPID) or equine insulin from a precursor peptide, so its Cushing’s disease (ECD)). plasma concentration indicates how much insulin is being produced by the pancreas. ACTH and cosyntropin (tetracosactide) The extent of β-cell loss can be deduced Corticotropin (ACTH) and cosyntropin (tet- from the result. Determining the amount racosactide) are used diagnostically to de- of C-peptide in diabetic animals allows for tect adrenal disorders, especially in dogs, therapeutic monitoring as one can dif- cats, and horses. Both peptides stimulate ferentiate between endogenous (produced the adrenal cortex (zona fasciculata) and by the body) and exogenous (injected into induce the production of glucocorticoids. the body) insulin. Inappropriate dosage of The use of cosyntropin is indicated in case insulin in dogs with low blood sugar levels of allergic reactions to the natural hor- results in a low C-peptide level. mone. In dogs, blood samples have to be Whereas type 1 diabetes is quite com- taken preceding the intravenous or intra- mon in dogs, type 2 diabetes has not been muscular injection of the peptide to obtain observed yet. the basal cortisol value, and one hour after In case of insulin resistance, the increased the administration. concentration of C-peptide results from a Canine Cushing’s disease (hyperadreno- high activity level of the pancreas β-cells. corticism, rather common in dogs but oc- Abnormally high amounts of C-peptide can curs rarely in cats) and Addison’s disease indicate the formation of an insulinoma (hypoadrenocorticism, in cats and dogs) which secretes insulin. can both be diagnosed. In case of spon- taneous hyperadrenocorticism, the ACTH Octreotide and analogs test is also performed to monitor the ef- Octreotide, a synthetic somatostatin ana- fects of medication. log showing higher activity and increased In neonatal foals, cosyntropin stimulation
6 is a reliable test for dysfunctions of the Antimicrobial peptides In the management of hypothalamic-pituitary-adrenal axis. An alternative to the antibiotics used in ani- cancer and develop- mals involved in food production may come ment of new (peptide) therapeutics, human Ceruletide from antimicrobial peptides, which have patients can profit from Ceruletide (caerulein) has been proposed been described in many organisms. These the experience gained as a diagnostic of hepatic dysfunctions peptides have a wide spectrum of action. with afflicted pet dogs in dogs. The cholecystokinin (CCK) analog They can kill gram negative and gram posi- and vice versa, as natu- stimulates postprandial serum bile acid, tive bacteria, enveloped viruses, yeasts, and rally occurring cancers and is a more efficient secretagogue than moulds. Several peptides were recently dis- in these species share CCK. As hepatopathy can occur in dogs covered in shrimp and oysters, where they many features includ- ing biological behavior suffering from severe respiratory diseases, are essential elements of innate defense, in and the response to administration of ceruletide as a liver func- the absence of acquired immunity. conventional therapies. tion test should be performed routinely with These molecules could advantageously such patients. replace antibiotics, since they are less sus- ceptible to cause resistance in the target microorganisms, due to their direct action Prospective Peptide Drugs on membranes, and to their fast degrad- ability, which avoid the accumulation of Peptide drugs residues. Peptide drugs such as exenatide or teripa- Application of antibacterial peptides is ratide, which have been successfully estab- an attractive option for intensive animal lished in human medicine, can likely also be husbandry such as poultry farming and, applied to treat similar medical conditions especially, aquaculture. of companion animals and horses. The somatostatin analogs lanreotide and the recently approved pasireotide also show potential in veterinary medicine, e.g. in the treatment of canine Cushing’s dis- ease or feline hypersomatotropism. In the management of cancer and develop- ment of new (peptide) therapeutics, human patients can profit from the experience gained with afflicted pet dogs and vice versa, as naturally occurring cancers in these species share many features includ- ing biological behavior and the response to conventional therapies.
Peptide vaccines Peptide-based vaccines could be a safer alternative to immunization using the inactivated virus. Peptide vaccines present a number of advantages, as they are easily available (also on large scale), relatively cheap, shelf-stable, chemically well-defined compounds. A number of studies evaluating synthetic peptides (immunogenic sequenc- es from viral proteins, used in combination with a suitable adjuvant for inoculation) as vaccines against viral diseases affecting livestock such as foot-and-mouth disease or swine fever have been published.
7 Peptides in Veterinary Medicine
REFERENCES
LHRH (GnRH) and Analogs T.E. Adams Using gonadotropin-releasing hormone LHRH and LHRH agonists (GnRH) and GnRH analogs to modulate tes- tis function and enhance the productivity of G.I. McRae et al. domestic animals. Long-term reversible suppression of Anim. Reprod. Sci. 88, 127-139 (2005) oestrus in bitches with nafarelin acetate, a potent LHRH agonist. C.A. Herbert and T.E. Trigg J. Reprod. Fertil. 74, 389-397 (1985) Applications of GnRH in the control and management of fertility in female animals. M.A. Crowe et al. Anim. Reprod. Sci. 88, 141-153 (2005) Induced ovulation of the first postpartum dominant follicle in beef suckler cows using M.A. Kutzler a GnRH analogue. Induction and synchronization of estrus in J. Reprod. Fertil. 99, 551-555 (1993) dogs. Theriogenology 64, 766-775 (2005) B.W. Knol et al. GnRH in the male dog: dose-response rela- A.M. Padula tionships with LH and testosterone. GnRH analogues - agonists and antago- J. Reprod. Fertil. 98, 159-161 (1993) nists. Anim. Reprod. Sci. 88, 115-126 (2005) A. Okada et al. Effects of dosage and treatment phase of S.E. Recabarreni et al. two GnRH analogues at the estrous stage Response to the gonadotropin releasing on superovulation in ewes. hormone agonist leuprolide in immature J. Reprod. Devel. 47, 275-281 (2001) female sheep androgenized in utero. Biol. Res. 38, 235-244 (2005) T.E. Trigg et al. Use of a GnRH analogue implant to pro- C. Gobello duce reversible long-term suppression of Dopamine agonists, anti-progestins, reproductive function in male and female anti-androgens, long-term-release GnRH domestic dogs. agonists and anti-estrogens in canine re- J. Reprod. Fertil. Suppl. 57, 255-261 (2001) production: a review. Theriogenology 66, 1560-1567 (2006) M.J. D’Occhio et al. Use of GnRH agonist implants for long-term M. Kutzler and A. Wood suppression of fertility in extensively man- Non-surgical methods of contraception and aged heifers and cows. sterilization. Anim. Reprod. Sci. 74, 151-162 (2002) Theriogenology 66, 514-525 (2006)
M.F. Martínez et al. L. Munson The effects of 3 gonadorelin products on Contraception in felids. luteinizing hormone release, ovulation, and Theriogenology 66, 126-134 (2006) follicular wave emergence in cattle. Can. Vet. J. 44, 125-131 (2003) F. Schneider et al. Endocrine, morphological, and cytological effects of a depot GnRH agonist in bovine. Anim. Reprod. Sci. 92, 9-28 (2006)
8 F. Schneider et al. E. Klaphake et al. Peptide drugs have Gonadotropin-releasing hormone (GnRH) Effects of leuprolide acetate on selected also found use in the treatment of compan- and its natural analogues: a review. blood and fecal sex hormones in Hispanio- ion animals and riding Theriogenology 66, 691-709 (2006) lan Amazon parrots (Amazona ventrais). horses, as their owners J. Avian Med. Surg. 23, 253-262 (2009) are increasingly will- F. Schneider and K.P. Brüssow ing to pay for expen- Effects of a preovulatory administered R. Thomassen and W. Farstad sive medication and depot gonadotrophin-releasing hormone Artificial insemination in canids: a useful therapies to prolong agonist on reproductive hormone levels and tool in breeding and conservation. or ameliorate the life of their diseased pets. pregnancy outcome in gilts. Theriogenology 71, 190-199 (2009) Peptides are used in the Reprod. Fertil. Dev. 18, 857-866 (2006) diagnosis and manage- Anti-GnRH vaccines ment of diabetes and T.E. Trigg et al. cancer which in recent A review of advances in the use of the F.R. Dunshea et al. years have become a GnRH agonist deslorelin in control of Vaccination of boars with a GnRH vac- growing problem with reproduction. cine (Improvac) eliminates boar taint and dogs and cats due to their increasing life Theriogenology 66, 1507-1512 (2006) increases growth performance. expectancy in combina- J. Anim. Sci. 79, 2524-2535 (2001) tion with obesity. E.U. Baitlesov et al. Additionally, vaccines Etiology and pathogenesis of ovarian cysts J.K. Levy et al. based on synthetic in cows and possibility of normalizing ovar- GnRH immunocontraception of male cats. peptides could become ian function. Theriogenology 62, 1116-1130 (2004) a viable alternative to Russ. Agric. Sci. 33, 260-263 (2007) vaccines obtained from viruses. L.A. Miller et al. K.P. Brüssow et al. Contraception of bison by GnRH vaccine: a Luteinizing hormone release after admin- possible means of decreasing transmission istration of the gonadotropin-releasing of brucellosis in bison. hormone agonist Fertilan (goserelin) for J. Wildl. Dis. 40, 725-730 (2004) synchronization of ovulation in pigs. J. Anim. Sci. 85, 129-137 (2007) G. Killian et al. Immunocontraception of Florida feral swine C. Gobello with a single-dose GnRH vaccine. New GnRH analogs in canine reproduction. Am. J. Reprod. Immunol. 55, 378-384 (2006) Anim. Reprod. Sci. 100, 1-13 (2007) Ovsynch M.A. Kutzler Estrus induction and synchronization in J.R. Pursley et al. canids and felids. Synchronization of ovulation in dairy cows Theriogenology 68, 354-374 (2007) using PGF2α and GnRH. Theriogenology 44, 915-923 (1995) L.C. Metrione et al. Preliminary evaluation of deslorelin, a GnRH H. Twagiramungu et al. agonist for contraception of the captive Synchronization of ovarian follicular waves variable flying fox Pteropus hypomelanus. with a gonadotropin-releasing hormone Contraception 78, 336-345 (2008) agonist to increase the precision of estrus in cattle: a review. J. Anim. Sci. 73, 3141-3151 (1995)
9 Peptides in Veterinary Medicine
R.L. Nebel and S.M. Jobst J. Taponen Evaluation of systematic breeding programs Fixed-time artificial insemination in beef for lactating dairy cows: a review. cattle. J. Dairy Sci. 81, 1169-1174 (1998) Acta Vet. Scand. 51, 48 (2009)
P.S. Baruselli et al. Ö.A. Öztürk et al. The use of hormonal treatments to improve Is Doublesynch protocol a new alternative reproductive performance of anestrous for timed artificial insemination in anes- beef cattle in tropical climates. trous dairy cows. Anim. Reprod. Sci. 82-83, 479-486 (2004) Theriogenology 73, 568-576 (2010)
A.R. Rabiee et al. GnRH in aquaculture Efficacy of Ovsynch program on reproduc- tive performance in dairy cattle: a meta- H.R. Lin et al. analysis. Effects of (sGnRH-A) and [D-Arg6, Trp 7, Leu8, J. Dairy Sci. 88, 2754-2770 (2005) Pro9NEt]-luteinizing hormone-releasing hormone (LHRH-A), in combination with N.M. Bello et al. pimozide or domperidone, on gonadotropin Optimizing ovulation to first GnRH improved release and ovulation in the Chinese loach outcomes to each hormonal injection of and common carp. ovsynch in lactating dairy cows. Gen. Comp. Endocrinol. 69, 31-40 (1988) J. Dairy Sci. 89, 3413-3424 (2006) Y. Zohar M.G. Colazo et al. Endocrinology and fish farming: aspects in Resynchronization of estrus in beef cattle: reproduction, growth, and smoltification. Ovarian function, estrus and fertility follow- Fish Physiol. Biochem. 7, 395-405 (1989) ing progestin treatment and treatments to synchronize ovarian follicular development C.R. Kramer et al. and estrus. sGnRH-A [(D-Arg6, Pro9 NEt-)LHRH] in com- Can. Vet. J. 48, 49-56 (2007) bination with domperidone induces gonad reversal in a protogynous fish, the bluehead W.W. Thatcher and J.E. Santos wrasse, Thalassoma bifasciatum. Control of ovarian follicular and corpus lu- J. Fish Biol. 42, 185-195 (1993) teum development for the synchronization of ovulation in cattle. H.R. Lin and R.E. Peter Soc. Reprod. Fertil. Suppl. 64, 69-81 (2007) Hormones and spawning in fish. Asian Fish. Sci. 9, 21-33 (1996) J.W. Lauderdale ASAS centennial paper: Contributions in the C.C. Mylonas and Y. Zohar Journal of Animal Science to the develop- Use of GnRHa-delivery systems for the ment of protocols for breeding management control of reproduction in fish. of cattle through synchronization of estrus Rev. Fish Biol. Fish. 10, 463-491(2001) and ovulation. J. Anim. Sci. 87, 801-812 (2009) Y. Zohar and C.C. Mylonas Endocrine manipulations of spawning in T. Osawa et al. cultured fish: from hormones to genes. Effect of synchronisation of ovulation on Aquaculture 197, 99-136 (2001) ovarian profile and days open in holstein cows diagnosed as nonpregnant 26 days E. Brzuska et al. after timed artificial insemination. The application of [D-Tle6,ProNHEt9]mGnRH J. Reprod. Devel. 55, 163-169 (2009) (Lecirelin) with the dopaminergic inhibitor metoclopramide to stimulate ovulation in African catfish (Clarias gariepinus). Czech J. Anim. Sci. 49, 297-306 (2004)
10 V.R. Cerqueira and M.Y. Tsuzuki Oxytocin and Carbetocin Contrary to mammals A review of spawning induction, larvicul- and other classes of ture, and juvenile rearing of the fat snook, J.R. Owiny et al. species, the sequences of GnRH I-III found Centropomus parallelus. Effect of pulsatile intravenous oxytocin ad- in fish show a high Fish Physiol. Biochem. 35, 17-28 (2009) ministration to pregnant sheep over the last diversity. third of gestation on fetal ACTH and cortisol C. Gillet and B. Breton responses to hypotension. LH secretion and ovulation following expo- J. Soc. Gynecol. Investig. 2, 13-18 (1995) sure of Arctic charr to different temperature and photoperiod regimes: responsiveness J.W. Lemaster et al. of females to a gonadotropin-releasing hor- Effects of administration of oxytocin on mone analogue and a dopamine antagonist. embryonic survival in progestogen supple- Gen. Comp. Endocrinol. 162, 210-218 (2009) mented cattle. Prostaglandins Other Lipid Mediat. 57, 259- S. Dufour et al. 268 (1999) Neuroendocrine control by dopamine of teleost reproduction. T.A.E. Stout et al. J. Fish Biol. 76, 129-160 (2010) Oxytocin administration prolongs luteal function in cyclic mares. C.C. Mylonas et al. J. Reprod. Fertil. 116, 315-320 (1999) Broodstock management and hormonal manipulation of fish reproduction. S. Gutjahr et al. Gen. Comp. Endocrinol. 165, 516-534 (2010) Effect of dose and day of treatment on uter- ine response to oxytocin in mares. GnRH antagonists Theriogenology 54, 447-456 (2000)
A.M. Hinojosa et al. J. Riedl et al. The effect of a GnRH antagonist on endo- Aetiology of reduced milk ejection in cows crine and seminal parameters in stallions. after transport and the use of a long-acting Theriogenology 56, 903-912 (2001) analogue of oxytocin for prophylaxis. (Antarelix) Vet. Rec. 148, 653-656 (2001)
H. Ulker et al. A.C. Bajcsy et al. LHRH antagonist decreases LH and proges- The effect of a single oxytocin or carbetocin terone secretion but does not alter length of treatment on uterine contractility in early estrous cycle in heifers. postpartum dairy cows. J. Anim. Sci. 79, 2902-2907 (2001) Theriogenology 65, 400-414 (2006) (Cetrorelix) D. Mota-Rojas et al. M.J. Evans et al. Comparative routes of oxytocin administra- Effectiveness of an antagonist to gonado- tion in crated farrowing sows and its effects trophin releasing hormone on the FSH and on fetal and postnatal asphyxia. LH response to GnRH in perifused equine Anim. Reprod. Sci. 92, 123-143 (2006) pituitary cells, and in seasonally acyclic mares. A.R. Schramme et al. Anim. Reprod. Sci. 73, 37-51 (2002) Pharmacokinetics of carbetocin, a long-act- (Cetrorelix) ing oxytocin analogue, following intravenous administration in horses. K.M. Pelican et al. Equine Vet. J. 40, 658-661 (2008) Short term suppression of follicular recruit- ment and spontaneous ovulation in the A.J. Barrett et al. cat using levonorgestrel versus a GnRH Effects of the administration of oxytocin or antagonist. carbetocin to dairy cows at parturition on Gen. Comp. Endocrinol. 144, 110-121 (2005) their subsequent fertility. (Antide) Vet. Rec. 165, 623-626 (2009)
11 Peptides in Veterinary Medicine
Vasopressin and Desmopressin G.A. Hermo et al. Effect of adjuvant perioperative desmo- P.A. van Wijk et al. pressin in locally advanced canine mamma- Responsiveness to corticotropin-releasing ry carcinoma and its relation to histologic hormone and vasopressin in canine Cush- grade. ing’s syndrome. J. Am. Anim. Hosp. Assoc. 47, 21-27 (2011) Eur. J. Endocrinol. 130, 410-416 (1994) Glucagon, Peptides in Pancreatic Disor- V. Bizub and L. Leng ders The effect of the long-term administration of vasopressin on the development of the Glucagon, C-peptide (diabetes) kidneys of growing lambs. Res. Vet. Sci. 62, 189-190 (1997) K. Yasuda et al. Exocrine pancreatic function in diabetic M.B. Callan and U. Giger dogs. Effect of desmopressin acetate administra- Jpn. J. Vet. Sci. 50, 1271-1273 (1988) tion on primary hemostasis in Doberman Pinschers with type-1 von Willebrand T.M. Montgomery et al. disease as assessed by a point-of-care Basal and glucagon-stimulated plasma instrument. C-peptide concentrations in healthy dogs, Am. J. Vet. Res. 63, 1700-1706 (2002) dogs with diabetes mellitus, and dogs with hyperadrenocorticism. C.A. Schmittinger et al. J. Vet. Intern. Med. 10, 116-122 (1996) Cardiopulmonary resuscitation with vaso- pressin in a dog. J.R. Fischer et al. Vet. Anaesth. Analg. 32, 112-114 (2005) Glucagon constant-rate infusion: a novel strategy for the management of hyperinsu- A.R. Hollis et al. linemic-hypoglycemic crisis in the dog. Plasma aldosterone, vasopressin and atrial J. Am. Anim. Hosp. Assoc. 36, 27-32 (2000) natriuretic peptide in hypovolaemia: a pre- liminary comparative study of neonatal and J.S. Rand et al. mature horses. Canine and feline diabetes mellitus: Nature Equine Vet. J. 40, 64-69 (2008) or nurture? J. Nutr. 134, 2072S-2080S (2004) S.J. Plunkett and M. McMichael Cardiopulmonary resuscitation in small T. Fall et al. animal medicine: an update. Diabetes mellitus in a population of 180,000 J. Vet. Intern. Med. 22, 9-25 (2008) insured dogs: incidence, survival, and breed distribution. F. Zeugswetter et al. J. Vet. Intern. Med. 21, 1209-1216 (2007) The desmopressin stimulation test in dogs with Cushing’s syndrome. T. Fall et al. Domest. Anim. Endocrinol. 34, 254-260 Glucagon stimulation test for estimating (2008) endogenous insulin secretion in dogs. Vet. Rec. 163, 266-270 (2008) R.D. Scroggin Jr. and J. Quandt The use of vasopressin for treating vasodi- L.M. Fleeman et al. latory shock and cardiopulmonary arrest. Pharmacokinetics and pharmacodynamics J. Vet. Emerg. Crit. Care (San Antonio) 19, of porcine insulin zinc suspension in eight 145-157 (2009) diabetic dogs. Vet. Rec. 164, 232-237 (2009)
12 R.S. Hess C. Khanna et al. Insulin resistance in dogs. A randomized controlled trial of octreotide Vet. Clin. North Am. Small Anim. Pract. 40, pamoate long-acting release and carbopla- 309-316 (2010) tin versus carboplatin alone in dogs with naturally occurring osteosarcoma: evalua- Glucagon (Hepatic Steatosis) tion of insulin-like growth factor suppres- sion and chemotherapy. A.R. Hippen et al. Clin. Cancer Res. 8, 2406-2412 (2002) Alleviation of fatty liver in dairy cows with 14-day intravenous infusions of glucagon. J.H. Robben et al. J. Dairy Sci. 82, 1139-1152 (1999) Comparison of ultrasonography, computed tomography, and single-photon emission A.R. Hippen computed tomography for the detection and Glucagon as a potential therapy for ketosis localization of canine insulinoma. and fatty liver. J. Vet. Intern. Med. 19, 15-22 (2005) Vet. Clin. North Am. Food Anim. Pract. 16, 267-282 (2000) J.H. Robben et al. Effect of octreotide on plasma concentra- R.A. Nafikov et al. tions of glucose, insulin, glucagon, growth Prevention of fatty liver in transition dairy hormone, and cortisol in healthy dogs and cows by subcutaneous injections of gluca- dogs with insulinoma. gon. Res. Vet. Sci. 80, 25-32 (2006) J. Dairy Sci. 89, 1533-1545 (2006) L.I. Slingerland et al. G. Bobe et al. Growth hormone excess and the effect of Exogenous glucagon effects on health and octreotide in cats with diabetes mellitus. reproductive performance of lactating dairy Domest. Anim. Endocrinol. 35, 352-361 cows with mild fatty liver. (2008) Anim. Reprod. Sci. 102, 194-207 (2007) U. Oberkirchner et al. M.A. Osman et al. Successful treatment of canine necrolytic Acute metabolic responses of postpartal migratory erythema (superficial necrolytic dairy cows to subcutaneous glucagon injec- dermatitis) due to metastatic glucagonoma tions, oral glycerol, or both. with octreotide. J. Dairy Sci. 91, 3311-3322 (2008) Vet. Dermatol. 21, 510-516 (2010)
Octreotide and analogs Diagnostics
K.W. Simpson et al. TRH Evaluation of the long-acting somatostatin analogue octreotide in the management of A. Burkhard and W. Kraft insulinoma in three dogs. [The thyrotropin-releasing hormone (TRH) J. Small Anim. Pract. 36, 161-165 (1995) test in the dog: injection or infusion?] Tierärztl. Prax. 22, 159-164 (1994) M. Altschul et al. Evaluation of somatostatin analogues for B.P. Meij et al. the detection and treatment of gastrinoma Thyroid-stimulating hormone responses in a dog. after single administration of thyrotropin- J. Small Anim. Pract. 38, 286-291 (1997) releasing hormone and combined admin- istration of four hypothalamic releasing hormones in beagle dogs. Domest. Anim. Endocrinol. 13, 465-468 (1996)
13 Peptides in Veterinary Medicine
B.P. Meij et al. ACTH and tetracosactide Residual pituitary function after trans- sphenoidal hypophysectomy in dogs with H. Eiler et al. pituitary-dependent hyperadrenocorticism. Adrenal gland function in the horse: effects J. Endocrinol. 155, 531-539 (1997) of cosyntropin (synthetic) and corticotropin (natural) stimulation. M.M. Diaz-Espiñeira et al. Am. J. Vet. Res. 40, 724-726 (1979) Thyrotropin-releasing hormone-induced growth hormone secretion in dogs with M.E. Peterson and R.J. Kemppainen primary hypothyroidism. Comparison of the immunoreactive plasma Domest. Anim. Endocrinol. 34, 176-181 corticotropin and cortisol responses to two (2008) synthetic corticotropin preparations (tetracosactrin and cosyntropin) in healthy TRH (Equine Cushing’s disease) cats. Am. J. Vet. Res. 53, 1752-1755 (1992) F.M. Andrews et al. Diagnosis of pituitary adenoma by using a L.A. Frank and J.W. Oliver combined dexamethasone suppression and Comparison of serum cortisol concentra- TRH stimulation test. tions in clinically normal dogs after admin- AAEP Proc. 43, 349-351 (1997) istration of freshly reconstituted versus reconstituted and stored frozen cosyntro- M.T. Donaldson et al. pin. Treatment with pergolide or cyproheptadine J. Am. Vet. Med. Assoc. 212, 1569-1571 of pituitary pars intermedia dysfunction (1998) (equine Cushing’s disease). J. Vet. Intern. Med. 16, 742-746 (2002) L.A. Frank et al. Cortisol concentrations following stimula- H.C. Schott 2nd tion of healthy and adrenopathic dogs with Pituitary pars intermedia dysfunction: two doses of tetracosactrin. equine Cushing’s disease. J. Small Anim. Pract. 41, 308-311 (2000) Vet. Clin. North Am. Equine Pract. 18, 237- 270 (2002) J.C. Ousey et al. Effects of maternally administered depot C.M. McGowan and R. Neiger ACTH(1-24) on fetal maturation and the tim- Efficacy of trilostane for the treatment of ing of parturition in the mare. equine Cushing’s syndrome. Equine Vet. J. 32, 489-496 (2000) Equine Vet. J. 35, 414-418 (2003) J.P. Schoeman et al. D. McFarlane et al. Cortisol response to two different doses of Alpha-melanocyte stimulating hormone intravenous synthetic ACTH (tetracosactrin) release in response to thyrotropin releasing in overweight cats. hormone in healthy horses, horses with J. Small Anim. Pract. 41, 552-557 (2000) pituitary pars intermedia dysfunction and equine pars intermedia explants. S. Paltrinieri et al. Domest. Anim. Endocrinol. 30, 276-288 Effect of 1-24 ACTH administration on (2006) sheep blood granulocyte functions. Vet. Res. 33, 71-82 (2002) J. Beech et al. Adrenocorticotropin concentration follow- L.A. Frank et al. ing administration of thyrotropin-releasing Steroid hormone concentration profiles in hormone in healthy horses and those with healthy intact and neutered dogs before pituitary pars intermedia dysfunction and and after cosyntropin administration. pituitary gland hyperplasia. Domest. Anim. Endocrinol. 24, 43-57 (2003) J. Am. Vet. Med. Assoc. 231, 417-426 (2007)
14 L.A. Frank et al. K.A. Hart et al. Serum concentrations of cortisol, sex Hypothalamic-pituitary-adrenal axis as- hormones of adrenal origin, and adrenocor- sessment in healthy term neonatal foals tical steroid intermediates in healthy dogs utilizing a paired low dose/high dose ACTH following stimulation with two doses of stimulation test. cosyntropin. J. Vet. Intern. Med. 23, 344-351 (2009) Am. J. Vet. Res. 65, 1631-1633 (2004) D.M. Wong et al. R.J. Kemppainen et al. Adrenocorticotropic hormone stimulation Use of compounded adrenocorticotropic tests in healthy foals from birth to 12 weeks hormone (ACTH) for adrenal function testing of age. in dogs. Can. J. Vet Res. 73, 65-72 (2009) J. Am. Anim. Hosp. Assoc. 41, 368-372 (2005) T.A. Cohen and E.C. Feldman E.N. Behrend et al. Comparison of IV and IM formulations of Intramuscular administration of a low dose synthetic ACTH for ACTH stimulation tests of ACTH for ACTH stimulation testing in in healthy dogs. dogs. J. Vet. Intern. Med. 26, 412-414 (2012) J. Am. Vet. Med. Assoc. 229, 528-530 (2006) P.J. Ginel et al. K.A. Hart et al. Evaluation of serum concentrations of Synthetic adrenocorticotropic hormone cortisol and sex hormones of adrenal gland stimulation tests in healthy neonatal foals. origin after stimulation with two synthetic J. Vet. Intern. Med. 21, 314-321 (2007) ACTH preparations in clinically normal dogs. Am. J. Vet. Res. 73, 237-241 (2012) Y. Hedberg et al. Effect of ACTH (tetracosactide) on steroid ACTH (Cushing’s disease) hormone levels in the mare. Part A: effect in intact normal mares and mares with pos- B. Meij et al. sible estrous related behavioral abnormali- Progress in transsphenoidal hypophysec- ties. tomy for treatment of pituitary-dependent Anim. Reprod. Sci. 100, 73-91 (2007) hyperadrenocorticism in dogs and cats. Mol. Cell. Endocrinol. 197, 89-96 (2002) Y. Hedberg et al. Effect of ACTH (tetracosactide) on steroid C.E. Reusch hormone levels in the mare. Part B: effect in Hyperadrencorticism. ovariectomized mares (including estrous In: Textbook of Veterinary Internal Medicine, behavior). Vol. II (S.J. Ettinger & E.C. Feldman, eds), W.B. Anim. Reprod. Sci. 100, 92-106 (2007) Saunders Co., Philadelphia (USA), 6th Ed., 1592-1612 (2005) L.G. Martin et al. Effect of low doses of cosyntropin on serum M.E. Peterson cortisol concentrations in clinically normal Diagnosis of hyperadrenocorticism in dogs. dogs. Clin. Tech. Small Anim. Pract. 22, 2-11 (2007) Am. J. Vet. Res. 68, 555-560 (2007) C.L. McLean J.P. Schoeman and M.E. Herrtage Management of Cushing’s syndrome in Adrenal response to the low dose ACTH dogs. stimulation test and the cortisol-to-adre- Vet. Rec. 165, 512 (2009) nocorticotrophic hormone ratio in canine babesiosis. Vet. Parasitol. 154, 205-213 (2008)
15 Peptides in Veterinary Medicine
ACTH (Addison’s disease) M. Paoloni and C. Khanna Translation of new cancer treatments from T.R. Famula et al. pet dogs to humans. Heritability and complex segregation analy- Nat. Rev. Cancer 8, 147-156 (2008) sis of hypoadrenocorticismin the standard poodle. C.C. Smith and C.K. Cebra J. Small Anim. Pract. 44, 8-12 (2003) Effects of exenatide on plasma glucose and insulin concentrations in alpacas. M.E. Herrtage J. Vet. Intern. Med. 23, 919-925 (2009) Hypoadrencorticism. In: Textbook of Veterinary Internal Medicine, V. Castillo et al. Vol. II (S.J. Ettinger & E.C. Feldman, eds), W.B. Effect of SOM230 (pasireotide) on cortico- Saunders Co., Philadelphia(USA), tropic cells: action in dogs with Cushing’s 6th Ed., 1612-1622 (2005) disease. Neuroendocrinology 94, 124-136 (2011) D.S. Greco Hypoadrenocorticism in small animals. C. Gilor et al. Clin. Tech. Small Anim. Pract. 22, 32-35 The GLP-1 mimetic exenatide potentiates (2007) insulin secretion in healthy cats. Domest. Anim. Endocrinol. 41, 42-49 (2011) P. Lathan et al. Use of a low-dose ACTH stimulation test for S. Niessen et al. diagnosis of hypoadrenocorticism in dogs. Pasireotide (SOM230) opens doors to J. Vet. Intern. Med. 22, 1070-1073 (2008) medical management of feline hyperso- matotropism. Ceruletide J. Vet. Intern. Med. 27, 685 (2013)
M. Rufer and E.G. Grünbaum C.K. Cebra et al. [Bile acid stimulation test with ceruletide.] Exenatide dosing in alpacas. Tierärztl. Prax. 25, 80-84 (1997) J. Vet. Pharmacol. Ther. 37, 417-420 (2014)
N.B. Bauer et al. C.J. Scudder et al. Liver disease in dogs with tracheal collapse. Pasireotide for the medical management of J. Vet. Intern. Med. 20, 845-849 (2006) feline hypersomatotropism. J. Vet. Intern. Med. 29, 1074-1080 (2015) N. Bridger et al. Comparison of postprandial and ceruletide Peptide vaccines serum bile acid stimulation in dogs. J. Vet. Intern. Med. 22, 873-878 (2008) J.H. Patarroyo et al. Immunization of cattle with synthetic pep- Prospective Peptide Drugs tides derived from the Boophilus microplus gut protein (Bm86). Peptide drugs Vet. Immunol. Immunopathol. 88, 163-172 (2002) A. Fuerst et al. Use of a parathyroid hormone peptide A.S. Beignon et al. (PTH(1-34))-enriched fibrin hydrogel for the A peptide vaccine administered transcuta- treatment of a subchondral cystic lesion neously together with cholera toxin elicits in the proximal interphalangeal joint of a potent neutralising anti-FMDV antibody warmblood filly. responses. J. Vet. Med. A Physiol. Pathol. Clin. Med. 54, Vet. Immunol. Immunopathol. 104, 273-280 107-112 (2007) (2005)
16 X.N. Dong et al. Non-Peptide Generic APIs Candidate multi-peptide-vaccine against classical swine fever virus induced potent Etomidate immunity with serological marker. Vaccine 23, 3630-3633 (2005) L.S. Pablo and J.E. Bailey Etomidate and telazol. E. Cox et al. Vet. Clin. North Am. Small Anim. Pract. 29, Adjuvants modulating mucosal immune 779-792 (1999) responses or directing systemic responses towards the mucosa. C.J. Broome and V.P. Walsh Vet. Res. 37, 511-539 (2006) Gastric dilatation-volvulus in dogs. NZ Vet. J. 51, 275-283 (2003) C.M. Hardy and A.L. Braid Vaccines for immunological control of fertil- L. Fresno et al. ity in animals. The effects on maternal and fetal cardio- Rev. Sci. Tech. 26, 461-470 (2007) vascular and acid-base variables after the administration of etomidate in the pregnant E.N.T. Meeusen et al. ewe. Current status of veterinary vaccines. Vet. J. 177, 94-103 (2008) Clin. Microbiol. Rev. 20, 489-510 (2007) J.M. Rodriguez et al. Antimicrobial peptides Comparison of the cardiopulmonary param- eters after induction of anaesthesia with A. Sarmasik alphaxalone or etomidate in dogs. Antimicrobial peptides: A potential thera- Vet. Anaesth. Analg. 39, 357-365 (2012) peutic alternative for the treatment of fish diseases. G.D. Readman et al. Turk. J. Biol. 26, 201-207 (2002) Do fish perceive anaesthetics as aversive? PLoS ONE 8, e73773 (2013) R.D. Joerger Alternatives to antibiotics: bacteriocins, S. Sanchis-Mora et al. antimicrobial peptides and bacteriophages. Anaesthetic management and complica- Poult. Sci. 82, 640-647 (2003) tions of pacemaker implantation in dogs. Vet. Rec. 175, 303 (2014) T. Dorrington and M. Gomez-Chiarri Antimicrobial peptides for use in oyster B. Qin et al. aquaculture: effect on pathogens, commen- Effects of continuous infusion of etomidate sals, and eukaryotic expression systems. at various dose rates on adrenal function in J. Shellfish Res. 27, 365-373 (2008) dogs. BMC Anesthesiol. 16, 2 (2016) A. Falco et al. Antimicrobial peptides as model molecules Propofol for the development of novel antiviral agents in aquaculture. C.E. Short and A. Bufalori Mini Rev. Med. Chem. 9, 1159-1164 (2009) Propofol anesthesia. Vet. Clin. North Am. Small Anim. Pract. 29, C.H. Li et al. 747-778 (1999) A review of advances in research on marine molluscan antimicrobial peptides and their G.L. Covey-Crump and P.J. Murison potential application in aquaculture. Fentanyl or midazolam for co-induction of Molluscan Res. 29, 17-26 (2009) anaesthesia with propofol in dogs. Vet. Anaesth. Analg. 35, 463-472 (2008)
17 Peptides in Veterinary Medicine
V. Andreoni et al. A. Cattai et al. Propofol and fentanyl infusions in dogs of The incidence of spontaneous movements various breeds undergoing surgery. (myoclonus) in dogs undergoing total intra- Vet. Anaesth. Analg. 36, 523-531 (2009) venous anaesthesia with propofol. Vet. Anaesth. Analg. 42, 93-8 (2015) R.J. Brosnan and E.P. Steffey Sedative effects of propofol in horses I. Cerasoli et al. Vet. Anaesth. Analg. 36, 421-425 (2009) The effects of intravenous lidocaine before propofol induction in premedicated dogs. K.E. Joubert J. Small Anim. Pract. 57, 435-40 (2016) Computer simulations of propofol infusions for total intravenous anaesthesia in dogs. H.X. Diao et al. J. S. Afr. Vet. Assoc. 80, 2-9 (2009) Comparison of the effects of propofol and emulsified isoflurane alone or combined K.R. Mama et al. with dexmedetomidine on induction of Multicenter clinical evaluation of a multi- anesthesia in dogs. dose formulation of propofol in the dog. Vet. Anaesth. Analg. 43, 145-52 (2016) BMC Vet. Res. 9, 261 (2013) E.A. Minghella et al. S. Sanchis-Mora et al. Clinical effects of midazolam or lidocaine Anaesthetic management and complica- co-induction with a propofol target-con- tions of pacemaker implantation in dogs. trolled infusion (TCI) in dogs. Vet. Rec. 175, 303 (2014) Vet. Anaesth. Analg. 43,472-81 (2016)
18 PEPTIDES FOR VETERINARY MEDICINE Peptide-based drugs are especially indicated for treating animals used in food production, as they are highly active compounds which require only very small doses. Additionally, they are metabolized more read- ily than organic compounds, which reduces the risk of contamination of the milk, eggs, or meat of the treated animal by the unmetabolized pharmaceutical and/or its degradation products.
19 Peptides in Veterinary Medicine
Gonadorelin Acetate Triptorelin Acetate LHRH CEP, DMF DMF GENERIC APIs H-4005-GMP, 4008614 H-4075-GMP, 4008442 Buserelin Triptorelin Pamoate DMF DMF H-4224-GMP, 4038785 H-6150-GMP, 4010246
Goserelin Acetate CEP, DMF H-6395-GMP, 4036062
Leuprolide Acetate CEP, DMF H-4060-GMP, 4008634
Desmopressin Acetate Octreotide Acetate FURTHER CEP, DMF DMF PEPTIDE H-7675-GMP, 4033038 H-5972-GMP, 4034264 Exenatide Pasireotide Acetate* GENERIC APIs DMF 4047875 4044219 *Bachem provides this product solely for pTH (1-34) (human) Acetate uses within the scope of any statute or law Glucagon DMF providing for an immunity, exemption, or DMF H-4835-GMP, 4033364 exception to patent infringement (“Exempt- H-6790-GMP, 4015466 ed Uses”), including but not limited to 35 U.S.C. § 271(e)(1) in the United States, the Tetracosactide Bolar type exemption in Europe, and any Lanreotide DMF corresponding exception to patent infringe- H-9055-GMP, 4071138 (Cosyntropin) ment in any other country. It is the sole H-1150-GMP, 4042686 responsibility of the purchaser or user of this product, and the purchaser or user of this product agrees to engage only in such Exempted Uses, and to comply with all ap- plicable intellectual property laws and/or regulations. The purchaser of this product agrees to indemnify Bachem against all claims in connection with the performance of the respective commercial agreement (e.g. supply agreement) and possible in- fringements of intellectual property rights.
For our complete offer of peptide and non-peptide generic APIs please order or download the catalog at our homepage www.bachem.com or go to http://www.bachem.com/api-products/generic-apis/
20 Etomidate NON-PEPTIDE CEP, DMF GENERIC APIs 2990-GMP, 4049295 Propofol CEP, DMF 2270-GMP, 40378086
21 Peptides in Veterinary Medicine RESEARCH GRADE PRODUCTS Bachem expressly draws attention to the fact that its products are intended for laboratory and research purposes only. Bachem therefore supplies such products only for the purposes of public research, experi- mental and teaching institutes, technical facilities and pertinent indus- trial units. Any exceptions (e.g. drug substances complying with GMP) are appropriately labeled.
Our research products can be found on our web site www.bachem.com: • Research Products Custom Synthesis Catalog Products Clinalfa Contact
22 10 6 13 7 LHRH (Des-Gly ,D-Leu ,[ C6]Leu ,Pro- LHRH ANALOGS (GnRH; Gonadorelin Acetate salt) NHEt9)-LHRH 13 7 H-4005 (([ C6]Leu )-Leuprolide) H-4224 H-4055 H-6395 this product agrees to engage only in such H-5936 LRPa-NH2 Exempted Uses, and to comply with all ap- 23 Peptides in Veterinary Medicine Carbetocin (Ile8)-Oxytocin OXYTOCIN, H-5832 (Mesotocin) Butyryl-YMe)IQNCPLG-NH2 H-2505 CYIQNCPIG-NH CARBETOCIN 2 Oxytocin (Disulfide bond) (RESEARCH H-2510 8 CYIQNCPLG-NH2 (Arg )-Vasotocin GRADE) (Disulfide bond) (Argiprestocin) H-1785 CYIQNCPRG-NH2 (Disulfide bond) (Arg8)-Vasopressin Deamino-Cys1, D-Arg8)-Vasopressin DESMOPRESSIN, (Argipressin; AVP) (Desmopressin; DDAVP) H-1780 H-7675 CYFQNCPRG-NH 3-Mercaptopropionyl-YFQNCPrG-NH VASOPRESSIN 2 2 (RESEARCH (Disulfide bond) (Disulfide bond) (Lys8)-Vasopressin GRADE) (Lypressin; LVP) H-2530 CYFQNCPKG-NH2 (Disulfide bond) Glucagon (1-29) (human, rat, porcine) Oxyntomodulin (human, mouse, rat) PEPTIDES IN H-6790 H-6058 HSQGTFTSDYSKYLDSRRAQD- HSQGTFTSDYSKYLDSRRAQD- PANCREATIC FVQWLMNT FVQWLMNTKRNRNNIA DISORDERS Glucagon (1-29) (human, rat, porcine) Oxyntomodulin (bovine, dog, porcine) Acetate salt H-6880 (RESEARCH H-7754 HSQGTFTSDYSKYLDSRRAQD- HSQGTFTSDYSKYLDSRRAQD- FVQWLMNTKRNKNNIA GRADE) FVQWLMNT (Tyr0)-C-Peptide (dog) 13 14 ([ C6]Leu )-Glucagon (1-29) H-2914 (human, rat, porcine) YEVEDLQVRDVELAGAPGEGGLQPLALE- H-7236 GALQ 13 HSQGTFTSDYSKY[ C6]LDSRRAQD- FVQWLMNT Octreotide H-5972 Biotinyl-Glucagon (1-29) (human, rat, fCFwKTC-L-threoninol porcine) (Disulfide bond) H-5676 3 Biotinyl-HSQGTFTSDYSKYLDSRRAQD- ([ring-D5]Phe )-Octreotide FVQWLMNT H-7238 fC[ring-D5 ]FwKTC-L-threoninol (Disulfide bond) 24 TRH Caerulein DIAGNOSTICS (Protirelin) (Ceruletide) H-4915 H-3220 Exenatide ([¹³C₆]Leu¹⁵)-pTH (1-34) (human) PROSPECTIVE (Exendin-4) H-7234 13 H-8730 SVSEIQLMHNLGKH [ C6] LNSMERVEW- DRUGS HGEGTFTSDLSKQMEEEAVRL- LRKKLQDVHNF FIEWLKNGGPSSGAPPPS-NH2 (RESEARCH pTH (1-84) (dog) Lanreotide H-6438 GRADE) H-9055 SVSEIQFMHNLGKHLSSMERVEWLRK- D-2Nal-CYwKVCT-NH₂ KLQDVHNFVALGAPIAHRDGSSQR- PLKKEDNVLVESYQKSLGEADKADVDVLT- Pasireotide* KAKSQ H-7542 C(Hyp(2-aminoethylcarbamoyl)-Phg- Ac-muramyl-Ala-D-Glu-NH2 wKY(Bzl)F) (MDP) G-1055 pTH (1-34) (human) MurNAc-Ae-NH2 (Teriparatide) H-4835 Palmitoyl-Cys((RS)-2,3- SVSEIQLMHNLGKHLNSMERVEWLRK- di(palmitoyloxy)-propyl)-Ser-Lys-Lys- KLQDVHNF Lys-Lys-OH H-5656 Pam3CSKKKK DL-Aminoglutethimide Xylazine (free base) NON-PEPTIDE Q-1020 Q-1445 DRUGS Phenserine Xylazine · HCl (RESEARCH- Q-1860 Q-1440 Vincamine base GRADE) Q-1435 25 Peptides in Veterinary Medicine All information is compiled to the best of our knowledge. We cannot be made liable for any possible errors or misprints. Furthermore, the terms of sales and delivery of the current main catalog are in force. 26 HEALTHY AND INFECTED COWS, THERMO- GRAMS Healthy and infected cows. Thermogram (infrared) images of a cow infected with the foot-and-mouth- disease virus (left) and a healthy cow (right). The effects of the disease cause the hooves to be hotter than usual, showing up on the thermogram as a red colour at left. For the uninfected cow at right, no heat or red colour is seen in the hooves. Foot-and-mouth disease is caused by viruses in the picornavirus group. It is highly contagious, spreading by direct contact with infected animals. Infected farm animals are slaughtered and burnt to remove contamination. KEYSTONE/SCIENCE PHOTO LIBRARY/ CRAIG PACKER/US DEPARTMENT OF AGRICULTURE 27 restricted countries. incertain or misprints. Someproducts may be made liable for any possible errors best of ourknowledge. We cannot be All information iscompiled to the shop.bachem.com or shoponline www.bachem.com Visit ourwebsite [email protected] +1 3105394171 Tel. +1 8884222436(toll free inUSA &Canada) Bachem Americas, Inc. Americas [email protected] Tel. +41585952020 Bachem AG Europe, Africa, Middle East andAsiaPacific Marketing &Sales Contact www.bachem.com shop .bachem.com 2009923 published by Global Marketing, Bachem Group, July 2017