WAY-100635和GR127935：对含5-羟色胺神经元的影响。

WAY-100635 and GR127935: effects on 5-hydroxytryptamine-containing neurones.

作者信息

Craven R, Grahame-Smith D, Newberry N

机构信息

University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.

出版信息

Eur J Pharmacol. 1994 Dec 12;271(1):R1-3. doi: 10.1016/0014-2999(94)90289-5.

DOI:10.1016/0014-2999(94)90289-5

PMID:7698189

Abstract

N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) is a potent and selective 5-HT1A receptor antagonist in a slice preparation of the guinea pig dorsal raphe nucleus: the inhibitory actions on 5-HT neuronal firing of 5-hydroxytryptamine (5-HT, serotonin), 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), but not those of baclofen, were abolished by 30 nM WAY-100635. The selective 5-HT1D receptor antagonist N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'- methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide (GR127935, 300 nM) did not attenuate the 5-HT induced inhibition, indicating that 5-HT1D receptors do not contribute to the inhibitory action of exogenous 5-HT on 5-HT neurones.

摘要

N-[2-[4-(2-甲氧基苯基)-1-哌嗪基]乙基]-N-(2-吡啶基)环己烷甲酰胺三盐酸盐（WAY-100635）在豚鼠背侧中缝核切片制备中是一种强效且选择性的5-羟色胺1A（5-HT1A）受体拮抗剂：30 nM的WAY-100635可消除5-羟色胺（5-HT，血清素）、5-羧酰胺色胺（5-CT）和8-羟基-2-(二正丙基氨基)四氢化萘（8-OH-DPAT）对5-HT神经元放电的抑制作用，但对巴氯芬的抑制作用无影响。选择性5-HT1D受体拮抗剂N-[4-甲氧基-3-(4-甲基-1-哌嗪基)苯基]-2'-甲基-4'-(5-甲基-1,2,4-恶二唑-3-基)[1,1-联苯]-4-甲酰胺（GR127935，300 nM）并未减弱5-HT诱导的抑制作用，这表明5-HT1D受体对外源性5-HT对5-HT神经元的抑制作用没有贡献。