DOCSLIB.ORG

Lisuride Reduces Psychomotor Retardation During Withdrawal from Chronic Intravenous Amphetamine Self-Administration in Rats Luigipulvirenti, M.D

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lisuride Reduces Psychomotor Retardation During Withdrawal from Chronic Intravenous Amphetamine Self-Administration in Rats Luigipulvirenti, M.D NEUROPSYCHOPHARMACOLOGY 1993- VOL. 8, NO.3 213 Lisuride Reduces Psychomotor Retardation during Withdrawal from Chronic Intravenous Amphetamine Self-Administration in Rats LuigiPulvirenti, M.D. and George F. Koob, Ph.D. Withdrawal from chronic use of psychostimulant drugs in behavioral changes, the effect of repeated treatment with hI/mans induces a clinical syndrome characterized by the nonaddictive ergot derivative lisuride during the fatigue, psychomotor depression, anhedonia, and withdrawal phase was evaluated. At a dose devoid of any disturbances of sleep. Spontaneous locomotor activity and effects on locomotor activity, lisuride completely CIIJIlepsy were assessed in rats during withdrawal from a prevented the reduction in locomotor activity and the rhedule of intravenous self-administration of high doses increase in catalepsy produced by amphetamine � amphetamine. At 2 and 4 days after cessation of withdrawal. These results suggest the need for further Imphetamine self-administration, rats showed a state of studies on lisuride as a possible novel treatment during psychomotor retardation as measured by reduction of withdrawal from psychostimulant drugs in humans. locomotor activity and increased catalepsy. In search of a [Neuropsychopharmacology 8:213-218, 1993J f»SSible pharmacologic means of intervention for such lEY WORDS: Amphetamine; Drug self-administration; with intense craving for the drug: such symptomatology Dopamine;Animal models of depression; Lisuride; usuallyencompasses various phases of withdrawal and Psychostimulant withdrawal lasts for a few weeks (Gawin and Kleber, 1986). Epi­ sodes of craving for the abused drug are particularly Thegrowth of psychostimulantdrug addiction in North pronounced and are considered to be one of the major America has reached epidemic proportions over the motivating factors leading to relapse in the addictive pastfew years. The parallel increase in the number of process. It is also believed that withdrawal dysphoria hospitaladmissions with such diagnoses has allowed may contribute, as a negative reinforcer, to drug­ nosologicalide ntifIcation and characterization of the seeking behavior. In accordance with this hypothesis, withdrawalsyndrome that follows abrupt discontinu­ it is possible that the neural substrates of the limbic fore­ ationo f the use of cocaine, amphetamine, or metham­ brain responsible for drug reward may also mediate, phetamine.The syndrome is mainly characterized by to some extent, withdrawal dysphoria (Pulvirentiet al. fatigue, depression of mood, anhedonia, psychomotor 1991). Finally, only tricyclic antidepressants have, to retardation, hypersomnia, and hyperphagia together date, proven clinically efficacious in reducing with­ drawal depression, with bromocriptine, a dopamine Fromthe Department of Neuropharmacology, The ScrippsResearch (DA) agonist, showing some efficacyin reducing crav­ Institute, LaJolla, California. ing for cocaine (Dackis and Gold 1985a; Gawin and Kle­ Addressreprint requests to: Luigi Pulvirenti, M.D., Biochemical ber 1984; Tennant and Sagherian 1987). Psychopharmacology Unit, "e. Mondino" Foundation, Department ciNeurology,University ofPavia, ViaPaiestro 3, Pavia 27100,ITALY. Lisuride is a nonaddictive ergot derivative known ReceivedAugus t 2, 1991; revised July 9, 1992; accepted July 15, 1992. to stimulate postsynaptic DA receptors (Uzumaki et al. e 1993American College of Neuropsychopharmacology Publishedby Elsevier Science Publishing Co., Inc. 6/i5Avenue of the Americas, New York, NY 10010 0893-133X/93/$6.00 214 L. Pulvirenti and G.F. Koob NEUROPSYCHOPHARMACOLOGY 1993- VOL. 8, NO.3 1982; Horowski and Wachtel 1976; Schechter 1984; attached to the polyethylene assembly mounted on the Rosenfeld and Makman 1981). In a recent study, it was animal's back immediately prior to the start of each ses­ suggested that lisuride may reduce intravenous cocaine sion. The cannula connector was removed following self-administration in rats (Pulvirenti and Koob submit­ the completion of a self-administration session and ted). This is in accordance with previous fIndings sug­ replaced with the guide cannula stylet. gesting a critical role for dopamine in the maintenance Four days following surgery, 14 rats were allowed of intravenous psychostimulant self-administration in 15-hour access every day (5:00 P.M. to 8:00 A.M.) for 10 various species (Markou and Koob 1992; Roberts and days to a metal lever mounted on the side wall of a stan­ Vickers 1984; Roberts et al. 1977, 1980). In addition, ex­ dard operant-conditioning cage. The cages themselves perimental and clinical studies have suggested that a were housed inside sound-attenuating chambers. A le­ state of DA depletion may occur during cocaine with­ ver press resulted in an intravenous injection of 0.1 ml drawal (Wyatt et al. 1988; Gawin and Kleber 1985; of d-amphetamine sulphate (0.12 mg/kg per injection, Dackis and Gold 1985b). A DA agonist would therefore or 0.325 J.1mollkg per injection) dissolved in 0.9% phys­ be expected to exert a normalizing action on the endog­ iologic saline and delivered over a period of 4 seconds. enous DA tone temporarily disrupted by repeated expo­ A swivel system allowed free movement of the animal sure to amphetamine. in the cage. Coincident with the onset of the injection, The aim of the present study was: 1) to quantify a stimulus light was illuminated for 20 seconds during the psychomotor retardation that follows withdrawal which time the lever pressing didnot result in reinforce­ from chronic intravenous self-administration of high ment. Lever presses during the period when the signal doses of amphetamine, and 2) to study the effect of light was not lit were reinforced on a continuous rein­ treatment with lisuride after drug discontinuation on forcement schedule. Control rats (n = 11) were injected such behavioral abnormalities. with an equal volume of passive intravenous physio­ The results presented here show that withdrawal logic saline infusion by an experimenter. from self-administration of high-dose intravenous am­ Following completion of the 10-day self-adminis­ phetamine induced reduction of spontaneous locomo­ tration period, spontaneous locomotor activity was tor activity and increased catalepsy, and the develop­ tested on days 1, 2, and 4 during withdrawal. Since loco­ ment of this syndrome was prevented by repeated motor testing was performed during the dark phase treatment with lisuride. (5:00 P.M. to 8:00 A.M.) and the last self-administration session ended at 8.00 A.M., day 1 of withdrawal actu­ ally corresponded to 33 hours after the end of intrave­ nous self-administration. Photobeam interruption was MATERIALS AND METHODS recorded for 180 minutes inphotocell cages as described Male Wistar rats (Charles River, Kingston, NY),weigh­ previously (Joyce and Koob 1981). ing between 200 and 225g at the start of the experiment, A separate group of 24 rats was used in the second were housed three to a cage and provided with ad part of the study. Sixteen rats were trained to self­ libitum access to food and water and maintained on administer amphetamine as described above; eight rats a 12-hour light/dark cycle (lights on from 4:00 A.M.- received experimentally administered saline as de­ 4:00 P.M.). scribed above. At the end of the 10-day self-admini­ Allanimals for self-administrationstudies were sur­ stration period, the amphetamine rats were treated with gically prepared under halothane anesthesia with a either lisuride (n = 8) (0.2 mg/kg IP, or 0.44 J.1mollkg) chronic silastic catheter implanted into the external or saline (n = 8) (1 ml/kg IP) twice daily at (8:00 A.M. jugular vein. The catheter/polyethylene assembly con­ and 8:00 P.M. for 4 days). sisted of silastic tubing attached to a guide cannula that For the study designed to test the effect of such was bent at a right angle. This junction was glued and repeated treatment with lisuride on spontaneous loco­ the guide cannula was embedded into a l-inch square motor activity in naive rats, four animals were injected of marlex mesh that was secured with silex. The cathe­ with one of four differentdoses of lisuride (0, 0.05, OJ, ter was passed subcutaneously from the rat's back to and 0.2 mg/kg IP, or 0, 0.11, 0.22, and 0.44 J.1mollkg, the jugular vein where it was implanted. The polyeth­ respectively, n = 16 rats) twice daily at 8:00 A.M. and ylene assembly was then mounted on the animal's back. 8:00 P.M. for 4 days. Animals were then tested as de­ A stylet was inserted into the guide cannula protrud­ scribed above. The injection schedule was chosen to ing from the animal's back to maintain a closed system avoid the peak effectof lisuride action during locomo­ and, therefore, prevent clogging of the cannula. tor testing. For self-administrationtesting, a cannula-connector Catalepsy testing was performed in the same rats assembly that was connected to a swivel and syringe during day 4 of withdrawal, at the end of the locomo­ pump as described by Roberts et al. (1977, 1980) was tor testing. Both forepaws of each rat were placed on KEUROPSYCHOPHARMACOLOGY 1993 - VOL. 8, NO. 3 Lisuride and Amphetamine Withdrawal 215 12 4 10· '0CII 3 .e �a 8 CII 0 E � 6 i= 2 • >- � <II C c. 4 CII f fti 7ii u 0 0 0 2 4 6 8 10 Control Amphetamine Day of IV Self-Administration Figure 3. Catalepsy time during withdrawal from chronic flprel. Amphetamine intake during daily IS-hour N self­ amphetamine self-administration in the same animals repre­ lllministration sessions. Values represent mean ± SEM for sented in Figure 2. The forepaws of each rat were placed on hats. The average intake was 7.37 mg/kg. a bar 9 cm from the floor. Values represent mean ± SEM of time elapsed until each rat (control: n = 11; amphetamine: n = 14) repositioned both forepaws on the floor. 'p < 0.05. i bar 9 cm from the floor. The time elapsed until each lit repositioned both forepaws on the floor was re­ activity was signifIcantlylower in rats withdrawing from corded by an experimenter blind to the treatment.
Load more

Recommended publications
  • Ergot Alkaloids Mycotoxins in Cereals and Cereal-Derived Food Products: Characteristics, Toxicity, Prevalence, and Control Strategies
    agronomy Review Ergot Alkaloids Mycotoxins in Cereals and Cereal-Derived Food Products: Characteristics, Toxicity, Prevalence, and Control Strategies Sofia Agriopoulou Department of Food Science and Technology, University of the Peloponnese, Antikalamos, 24100 Kalamata, Greece; [email protected]; Tel.: +30-27210-45271 Abstract: Ergot alkaloids (EAs) are a group of mycotoxins that are mainly produced from the plant pathogen Claviceps. Claviceps purpurea is one of the most important species, being a major producer of EAs that infect more than 400 species of monocotyledonous plants. Rye, barley, wheat, millet, oats, and triticale are the main crops affected by EAs, with rye having the highest rates of fungal infection. The 12 major EAs are ergometrine (Em), ergotamine (Et), ergocristine (Ecr), ergokryptine (Ekr), ergosine (Es), and ergocornine (Eco) and their epimers ergotaminine (Etn), egometrinine (Emn), egocristinine (Ecrn), ergokryptinine (Ekrn), ergocroninine (Econ), and ergosinine (Esn). Given that many food products are based on cereals (such as bread, pasta, cookies, baby food, and confectionery), the surveillance of these toxic substances is imperative. Although acute mycotoxicosis by EAs is rare, EAs remain a source of concern for human and animal health as food contamination by EAs has recently increased. Environmental conditions, such as low temperatures and humid weather before and during flowering, influence contamination agricultural products by EAs, contributing to the Citation: Agriopoulou, S. Ergot Alkaloids Mycotoxins in Cereals and appearance of outbreak after the consumption of contaminated products. The present work aims to Cereal-Derived Food Products: present the recent advances in the occurrence of EAs in some food products with emphasis mainly Characteristics, Toxicity, Prevalence, on grains and grain-based products, as well as their toxicity and control strategies.
    [Show full text]
  • Australian Product Information Parlodel® (Bromocriptine Mesilate)
    AUSTRALIAN PRODUCT INFORMATION PARLODEL® (BROMOCRIPTINE MESILATE) TABLET AND HARD CAPSULE 1 NAME OF THE MEDICINE Bromocriptine mesilate 2 QUALITATIVE AND QUANTITATIVE COMPOSITION • Parlodel tablets and capsules contain bromocriptine mesilate • Oral tablets: ➢ 2.5 mg bromocriptine (present as 2.9 mg mesilate). • Oral capsules: ➢ 10 mg bromocriptine (present as 11.5 mg mesilate). ➢ 5 mg bromocriptine (present at 5.735 mg mesilate). • List of excipients with known effect: lactose and sugars. • For the full list of excipients, see Section 6.1 List of excipients. 3 PHARMACEUTICAL FORM Oral tablets: • White, coded XC with breakline on one side, SANDOZ on the other side. Oral capsules: • 5 mg: opaque white and opaque blue, marked PS • 10 mg: opaque white 4 CLINICAL PARTICULARS 4.1 THERAPEUTIC INDICATIONS • Prevention of onset of lactation in the puerperium for clearly defined medical reasons. Therapy should be continued for 14 days to prevent rebound lactation. Parlodel should not be used to suppress established lactation. • Treatment of hyperprolactinaemia where surgery and/or radiotherapy are not indicated or have already been used with incomplete resolution. Precautions should be taken to ensure that the hyperprolactinaemia is not due to severe primary hypothyroidism. Where the cause of hyperprolactinaemia is a prolactin-secreting microadenoma or macroadenoma, Parlodel is indicated for conservative treatment; prior to surgery in order to reduce tumour size and to facilitate removal; after surgery if prolactin level is still elevated. • Adjunctive therapy in the management of acromegaly when: (1) The patient refuses surgery and/or radiotherapy (2) Surgery and/or radiotherapy has been unsuccessful or full effects are not expected for some months (3) A manifestation of the acromegaly needs to be brought under control pending surgery and/or radiotherapy.
    [Show full text]
  • Cabergoline Monograph
    Cabergoline DRUG NAME: Cabergoline SYNONYM(S): COMMON TRADE NAME(S): DOSTINEX® CLASSIFICATION: hormonal agent Special pediatric considerations are noted when applicable, otherwise adult provisions apply. MECHANISM OF ACTION: Cabergoline is a dopaminergic ergot derivative with longer lasting prolactin lowering activity than bromocriptine. Cabergoline may decrease hormone production and the size of prolactin-dependent pituitary adenomas1 by inhibiting the release and synthesis of prolactin from the anterior pituitary gland.2,3 The prolactin lowering effect is dose-related.2 PHARMACOKINETICS: Oral Absorption rapidly absorbed, unaffected by food Distribution widely distributed,4 time to peak 2-3 h, steady state achieved after 4 weeks cross blood brain barrier? yes volume of distribution no information found plasma protein binding 40-42% Metabolism extensive hepatic metabolism, primarily via hydrolysis with minimal CYP450 mediated metabolism; undergoes first-pass metabolism active metabolite(s) no information found inactive metabolite(s)4-6 eight metabolites including 6-allyl-8b-carboxy-ergoline Excretion primarily hepatic7 urine7 18-22%, <4% unchanged after 20 days feces7 60-72% after 20 days terminal half life 63-69 h, hyperprolactinemic patients: 79-115 h clearance no information found Sex no significant differences found7 Elderly no significant differences found7 Adapted from standard reference2 unless specified otherwise. USES: Primary uses: Other uses: *Pituitary tumours *Health Canada approved indication SPECIAL PRECAUTIONS: Contraindications2:
    [Show full text]
  • Schizophrenia Care Guide
    August 2015 CCHCS/DHCS Care Guide: Schizophrenia SUMMARY DECISION SUPPORT PATIENT EDUCATION/SELF MANAGEMENT GOALS ALERTS Minimize frequency and severity of psychotic episodes Suicidal ideation or gestures Encourage medication adherence Abnormal movements Manage medication side effects Delusions Monitor as clinically appropriate Neuroleptic Malignant Syndrome Danger to self or others DIAGNOSTIC CRITERIA/EVALUATION (PER DSM V) 1. Rule out delirium or other medical illnesses mimicking schizophrenia (see page 5), medications or drugs of abuse causing psychosis (see page 6), other mental illness causes of psychosis, e.g., Bipolar Mania or Depression, Major Depression, PTSD, borderline personality disorder (see page 4). Ideas in patients (even odd ideas) that we disagree with can be learned and are therefore not necessarily signs of schizophrenia. Schizophrenia is a world-wide phenomenon that can occur in cultures with widely differing ideas. 2. Diagnosis is made based on the following: (Criteria A and B must be met) A. Two of the following symptoms/signs must be present over much of at least one month (unless treated), with a significant impact on social or occupational functioning, over at least a 6-month period of time: Delusions, Hallucinations, Disorganized Speech, Negative symptoms (social withdrawal, poverty of thought, etc.), severely disorganized or catatonic behavior. B. At least one of the symptoms/signs should be Delusions, Hallucinations, or Disorganized Speech. TREATMENT OPTIONS MEDICATIONS Informed consent for psychotropic
    [Show full text]
  • Hallucinogens: a Cause of Convulsive Ergot Psychoses
    Loma Linda University TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works Loma Linda University Electronic Theses, Dissertations & Projects 6-1976 Hallucinogens: a Cause of Convulsive Ergot Psychoses Sylvia Dahl Winters Follow this and additional works at: https://scholarsrepository.llu.edu/etd Part of the Psychiatry Commons Recommended Citation Winters, Sylvia Dahl, "Hallucinogens: a Cause of Convulsive Ergot Psychoses" (1976). Loma Linda University Electronic Theses, Dissertations & Projects. 976. https://scholarsrepository.llu.edu/etd/976 This Thesis is brought to you for free and open access by TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works. It has been accepted for inclusion in Loma Linda University Electronic Theses, Dissertations & Projects by an authorized administrator of TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works. For more information, please contact [email protected]. ABSTRACT HALLUCINOGENS: A CAUSE OF CONVULSIVE ERGOT PSYCHOSES By Sylvia Dahl Winters Ergotism with vasoconstriction and gangrene has been reported through the centuries. Less well publicized are the cases of psychoses associated with convulsive ergotism. Lysergic acid amide a powerful hallucinogen having one.-tenth the hallucinogenic activity of LSD-25 is produced by natural sources. This article attempts to show that convulsive ergot psychoses are mixed psychoses caused by lysergic acid amide or similar hallucinogens combined with nervous system
    [Show full text]
  • Title Structure of the Human Histamine H1 Receptor Complex With
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Kyoto University Research Information Repository Structure of the human histamine H1 receptor complex with Title doxepin. Shimamura, Tatsuro; Shiroishi, Mitsunori; Weyand, Simone; Tsujimoto, Hirokazu; Winter, Graeme; Katritch, Vsevolod; Author(s) Abagyan, Ruben; Cherezov, Vadim; Liu, Wei; Han, Gye Won; Kobayashi, Takuya; Stevens, Raymond C; Iwata, So Citation Nature (2011), 475(7354): 65-70 Issue Date 2011-07-07 URL http://hdl.handle.net/2433/156845 © 2011 Nature Publishing Group, a division of Macmillan Right Publishers Limited. Type Journal Article Textversion author Kyoto University Title: Structure of the human histamine H1 receptor in complex with doxepin. Authors Tatsuro Shimamura 1,2,3*, Mitsunori Shiroishi 1,2,4*, Simone Weyand 1,5,6, Hirokazu Tsujimoto 1,2, Graeme Winter 6, Vsevolod Katritch7, Ruben Abagyan7, Vadim Cherezov3, Wei Liu3, Gye Won Han3, Takuya Kobayashi 1,2‡, Raymond C. Stevens3‡and So Iwata1,2,5,6,8‡ 1. Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. 2. Department of Cell Biology, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-Ku, Kyoto 606-8501, Japan. 3. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 4. Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. 5. Division of Molecular Biosciences, Membrane Protein Crystallography Group, Imperial College, London SW7 2AZ, UK. 6. Diamond Light Source, Harwell Science and Innovation Campus, Chilton, Didcot, Oxfordshire OX11 0DE, UK.
    [Show full text]
  • Ergot Alkaloid Biosynthesis in Aspergillus Fumigatus : Association with Sporulation and Clustered Genes Common Among Ergot Fungi
    Graduate Theses, Dissertations, and Problem Reports 2009 Ergot alkaloid biosynthesis in Aspergillus fumigatus : Association with sporulation and clustered genes common among ergot fungi Christine M. Coyle West Virginia University Follow this and additional works at: https://researchrepository.wvu.edu/etd Recommended Citation Coyle, Christine M., "Ergot alkaloid biosynthesis in Aspergillus fumigatus : Association with sporulation and clustered genes common among ergot fungi" (2009). Graduate Theses, Dissertations, and Problem Reports. 4453. https://researchrepository.wvu.edu/etd/4453 This Dissertation is protected by copyright and/or related rights. It has been brought to you by the The Research Repository @ WVU with permission from the rights-holder(s). You are free to use this Dissertation in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you must obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Dissertation has been accepted for inclusion in WVU Graduate Theses, Dissertations, and Problem Reports collection by an authorized administrator of The Research Repository @ WVU. For more information, please contact [email protected]. Ergot alkaloid biosynthesis in Aspergillus fumigatus: Association with sporulation and clustered genes common among ergot fungi Christine M. Coyle Dissertation submitted to the Davis College of Agriculture, Forestry, and Consumer Sciences at West Virginia University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Genetics and Developmental Biology Daniel G. Panaccione, Ph.D., Chair Kenneth P. Blemings, Ph.D. Joseph B.
    [Show full text]
  • Ergot Poisoning G
    Postgrad Med J: first published as 10.1136/pgmj.42.491.562 on 1 September 1966. Downloaded from POSTGRAD. MED. J. (1966), 42, 562. Case Reports ERGOT POISONING G. GLAZER, M.B., B.S. K. A. MYERS, M.B.(Melb.), F.R.A.C.S. House Surgeon, Surgical Unit. Senior Registrar, Surgical Unit (Smith and Nephew Fellow). E. R. DAVIES, M.B., M.R.C.P.E., F.F.R. Senior Registrar, Radiological Dept., St. Mary's Hospital, London, W.2. ERGOTAMINE tartrate is frequently prescribed for the Progress: Following admission the patient became treatment of migraine. Complications from the drug drowsy, nauseated and suffered from attacks of vertigo. are rare but potentially serious. Five days after cessation of ergotamine therapy the foot A case is presented of severe lower limb arterial pulses became palpable and he then developed intense spasm due to ergotamine tartrate taken sublingually and burning sensations in both feet (St. Anthony's Fire). orally for migraine. This case provided an opportunity It was considered that final confirmation of the to study the vascular and systemic effects of the drug and diagnosis necessitated reproduction of the symptoms the literature the manifes- with a small provocative dose of ergotamine. One day to review concerning risk, after the return of the foot pulses, ergotamine tartrate tations and treatment of ergot poisoning. was recommenced, and a total of 10 mg. was given orally Case Report over a period of three days; the foot pulses disappeared Mr. E.K., a 33 year old van-driver, presented in eighteen hours after the initial 2 mg.
    [Show full text]
  • Bromocriptine-A Changing Scene
    LONDON, SATURDAY 20 DECEMBER 1975 Br Med J: first published as 10.1136/bmj.4.5998.667 on 20 December 1975. Downloaded from MEDICAL JOURNAL Bromocriptine -a changing scene Ergot, known to man since ancient times, is a product of the Levodopa has been used to lower prolactin levels, but its fungus Claviceps purpurea that grows on rye and grain. A action does not last long enough; bromocriptine has a much symposium' at the Royal College of Physicians last May longer action and is therefore more effective. reviewed the pharmacology and clinical uses of the older as Since bromocriptine has been shown not to be teratogenic it well as the more recently introduced ergot compounds. All the has been used recently in restoring fertility. Its place has still ergot alkaloids are derivatives of lysergic acid: the best known finally to be defined, but it appears to be effective not only in are the oxytocic ergometrine and the mixed ao-adrenergic patients with hyperprolactinaemia but also in some with agonist and antagonist ergometrine compounds. Nevertheless, normal prolactin levels, as described by M 0 Thorner et al,14 the first group of ergot compounds isolated by Barger, Carr, at p 694 of this issue. There is, however, some danger in and Dale in 1906, and called ergotoxine,2 is a mixture of ergot restoring fertility in women with small pituitary tumours, alkaloids: ergocornine, ergocristine, and ergokryptine. since such lesions may rapidly enlarge, with visual impairment, The inhibition oflactation by ergot was described by Dodart3 during pregnancy. Arguably the tumour should be irradiated in 1676.
    [Show full text]
  • Natural Psychoplastogens As Antidepressant Agents
    molecules Review Natural Psychoplastogens As Antidepressant Agents Jakub Benko 1,2,* and Stanislava Vranková 1 1 Center of Experimental Medicine, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia; [email protected] 2 Faculty of Medicine, Comenius University, 813 72 Bratislava, Slovakia * Correspondence: [email protected]; Tel.: +421-948-437-895 Academic Editor: Olga Pecháˇnová Received: 31 December 2019; Accepted: 2 March 2020; Published: 5 March 2020 Abstract: Increasing prevalence and burden of major depressive disorder presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after several weeks of continuous treatment. In addition, their serious side effects and ineffectiveness in one-third of patients call for urgent action. Recent advances have given rise to the concept of psychoplastogens. These compounds are capable of fast structural and functional rearrangement of neural networks by targeting mechanisms previously implicated in the development of depression. Furthermore, evidence shows that they exert a potent acute and long-term positive effects, reaching beyond the treatment of psychiatric diseases. Several of them are naturally occurring compounds, such as psilocybin, N,N-dimethyltryptamine, and 7,8-dihydroxyflavone. Their pharmacology and effects in animal and human studies were discussed in this article. Keywords: depression; antidepressants; psychoplastogens; psychedelics; flavonoids 1. Introduction 1.1. Depression Depression is the most common and debilitating mental disease. Its prevalence and burden have been steadily rising in the past decades. For example, in 1990, the World Health Organization (WHO) projected that depression would increase from 4th to 2nd most frequent cause of world-wide disability by 2020 [1].
    [Show full text]
  • Drugs for Parkinson's Disease
    Australian Prescriber Vol. 24 No. 4 2001 Drugs for Parkinson’s disease V.S.C. Fung, M.A. Hely, Department of Neurology, G. De Moore, Department of Psychiatry and J.G.L. Morris, Department of Neurology, Westmead Hospital, Westmead, New South Wales SYNOPSIS Levodopa commonly causes nausea, especially when treatment Levodopa is the most effective drug available for treating begins. This nausea results from the conversion of levodopa to the motor symptoms of idiopathic Parkinson’s disease. It dopamine which stimulates the dopamine receptors in the area is usually combined with a peripheral dopa decarboxylase postrema (‘vomiting centre’) in the brainstem, a structure which inhibitor. Early treatment with dopamine agonists can lies outside the blood-brain barrier. The nausea is minimised by reduce the risk of developing dyskinesia. Dopamine agonists introducing levodopa slowly, starting with a low dose, taking it and catechol-O-methyltransferase inhibitors can with food and giving it in combination with a peripheral dopa significantly reduce motor fluctuations. Amantadine decarboxylase inhibitor such as carbidopa or benserazide. A reduces the severity of dyskinesia in some patients. No minimum daily dose of 75 mg is necessary to adequately inhibit treatment has been proven to delay disease progression. the production of dopamine outside the blood-brain barrier. Metoclopramide and prochlorperazine should be avoided as Index words: amantadine, dopamine, entacapone, they are dopamine antagonists and make parkinsonism worse. levodopa, selegiline. If an antiemetic is required, domperidone 10–20 mg three times (Aust Prescr 2001;24:92–5) daily is the drug of choice as it is a dopamine antagonist which does not cross the blood-brain barrier.
    [Show full text]
  • Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor
    pharmaceuticals Review Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor Qing Wang 1,2 , Yu Zhou 2 , Jianhui Huang 1 and Niu Huang 2,3,* 1 School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China; [email protected] (Q.W.); [email protected] (J.H.) 2 National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China; [email protected] 3 Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, China * Correspondence: [email protected]; Tel.: +86-10-80720645 Abstract: Since the first characterization of the 5-hydroxytryptamine 2B receptor (5-HT2BR) in 1992, significant progress has been made in 5-HT2BR research. Herein, we summarize the biological function, structure, and small-molecule pharmaceutical ligands of the 5-HT2BR. Emerging evidence has suggested that the 5-HT2BR is implicated in the regulation of the cardiovascular system, fibrosis disorders, cancer, the gastrointestinal (GI) tract, and the nervous system. Eight crystal complex structures of the 5-HT2BR bound with different ligands provided great insights into ligand recognition, activation mechanism, and biased signaling. Numerous 5-HT2BR antagonists have been discovered and developed, and several of them have advanced to clinical trials. It is expected that the novel 5-HT2BR antagonists with high potency and selectivity will lead to the development of first-in-class drugs in various therapeutic areas. Keywords: GPCR; 5-HT2BR; biased signaling; agonist; antagonist Citation: Wang, Q.; Zhou, Y.; Huang, J.; Huang, N. Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor. 1. Introduction Pharmaceuticals 2021, 14, 76.
    [Show full text]