5-HT(3) RECEPTOR ANTAGONISM BY ANPIRTOLINE, A MIXED 5-HT(1) RECEPTOR AGONIST 5-HT(3) RECEPTOR ANTAGONIST

Citation
M. Gothert et al., 5-HT(3) RECEPTOR ANTAGONISM BY ANPIRTOLINE, A MIXED 5-HT(1) RECEPTOR AGONIST 5-HT(3) RECEPTOR ANTAGONIST, British Journal of Pharmacology, 114(2), 1995, pp. 269-274
Citations number
35
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00071188
Volume
114
Issue
2
Year of publication
1995
Pages
269 - 274
Database
ISI
SICI code
0007-1188(1995)114:2<269:5RABAA>2.0.ZU;2-V
Abstract
1 The aim of this study was to provide evidence that anpirtoline, whic h is an agonist at 5-HT1B and 5-HT1D receptors and also displays submi cromolar affinity for 5-HT1A recognition sites, in addition, acts as a n antagonist at 5-HT3 receptors. 2 In radioligand binding studies on r at brain cortical membranes, anpirtoline inhibited specific binding of [H-3]-(S)-zacopride to 5-HT3 receptor recognition sites (pK(i): 7.53) . 3 In NlE-115 neuroblastoma cells in which [C-14]-guanidinium was use d as a tool to measure cation influx through the 5-HT3 receptor channe l, the 5-HT-induced influx was concentration-dependently inhibited by anpirtoline. In this respect, anpirtoline mimicked other 5-HT3 recepto r antagonists; the rank order of potency was ondansetron> anpirtoline> metoclopramide. 4 The concentration-response curve for 5-HT as a stim ulator of [C-14]-guanidinium influx was shifted to the right by anpirt oline (apparent pA(2): 7.78), 5 In urethane-anaesthetized rats, anpirt oline inhibited (at lower potency than zacopride and tropisetron) the 5-HT- or phenylbiguanide-induced bradycardia (Bezold-Jarisch reflex), but did not induce this reflex by itself. 6 Intravenous infusion of ci splatin in the domestic pig caused a consistent emetic response which was antagonized by anpirtoline. 7 It is concluded that anpirtoline, wh ich was previously characterized as a 5-HT1 receptor agonist also prov ed to be a 5-HT3 receptor antagonist in several experimental models an d, hence, exhibits a unique pattern of properties at different 5-HT re ceptors.