| Pharmacological characterization of the selective nonpeptide neuropeptide Y Y1 receptor antagonist BIBP 3226. | |
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MedLine Citation:
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PMID: 7562541 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The present study was undertaken to investigate the in vitro and in vivo pharmacological profile of the novel, nonpeptide neuropeptide Y (NPY) Y1-selective antagonist, BIBP 3226 [(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-am ide], and a recently described peptidic structure [Ile-Glu-Pro-Orn-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic (2,4'), (2',4)-diamide]. BIBP 3226 antagonized the NPY Y1 receptor-mediated decrease in the twitch response in the rabbit vas deferens preparation with a pKb value of 6.98 +/- 0.06 (n = 16). It showed no affinity (EC50 > 1 microM) for NPY Y2 receptors in the rat vas deferens. NPY-induced increases in perfusion pressure in the isolated perfused rat kidney and rabbit ear preparations were antagonized with IC50 values of 26.8 +/- 4.5 (n = 4) and 214 +/- 30 nM (n = 4), respectively. The NPY-mediated potentiation of the noradrenaline elicited increase in perfusion pressure in the rat mesenteric bed was antagonized with an IC50 value of 976 (542-1760) nM. The NPY-induced increase in blood pressure in the pithed rat was inhibited by BIBP 3226 dose-dependently (ED50 = 0.11 +/- 0.03 mg/kg i.v.), whereas no effect of BIBP 3226 (1 mg/kg i.v.) was observed for the noradrenaline-, angiotensin-, endothelin- or vasopressin-induced pressor response. The data presented demonstrate that BIBP 3226 is a competitive and NPY Y1-selective antagonist. The peptidic compound proved to possess high potency for NPY Y1 receptors, but showed both agonistic as well as antagonistic properties.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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H N Doods; W Wienen; M Entzeroth; K Rudolf; W Eberlein; W Engel; H A Wieland |
Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 275 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1995 Oct |
Date Detail:
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Created Date: 1995-11-21 Completed Date: 1995-11-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 136-42 Citation Subset: IM |
Affiliation:
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Dr. Karl Thomae GmbH, Biberach, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Arginine / analogs & derivatives*, pharmacology Blood Pressure / drug effects Dose-Response Relationship, Drug Kidney / blood supply, drug effects Male Molecular Sequence Data Muscle Contraction / drug effects Muscle, Smooth / drug effects, physiology Neuropeptide Y / analogs & derivatives, pharmacology Perfusion Rabbits Rats Rats, Inbred SHR Receptors, Neuropeptide Y / antagonists & inhibitors* Vas Deferens / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/BIBP 3226; 0/EXBP 68; 0/Neuropeptide Y; 0/Receptors, Neuropeptide Y; 74-79-3/Arginine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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