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
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.