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VETERINARY PEPTIDES Peptides in Veterinary Medicine

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VETERINARY PEPTIDES Peptides in Veterinary Medicine 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
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