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5‐HT 3 receptor antagonism by anpirtoline, a mixed 5‐HT 1 receptor agonist/5‐HT 3 receptor antagonist
Author(s) -
Göthert M.,
Hamon M.,
Barann M.,
Bönisch H.,
Gozlan H.,
Laguzzi R.,
Metzenauer P.,
Nickel B.,
Szelenyi I.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13222.x
Subject(s) - agonist , 5 ht receptor , receptor , chemistry , receptor antagonist , tropisetron , endocrinology , medicine , pharmacology , antagonist , serotonin , biology , biochemistry
1 The aim of this study was to provide evidence that anpirtoline, which is an agonist at 5‐HT 1B and 5‐HT 1D receptors and also displays submicromolar affinity for 5‐HT 1A recognition sites, in addition, acts as an antagonist at 5‐HT 3 receptors. 2 In radioligand binding studies on rat brain cortical membranes, anpirtoline inhibited specific binding of [ 3 H]‐(S)‐zacopride to 5‐HT 3 receptor recognition sites (p K i : 7.53). 3 In N1E‐115 neuroblastoma cells in which [ 14 C]‐guanidinium was used as a tool to measure cation influx through the 5‐HT 3 > receptor channel, the 5‐HT‐induced influx was concentration‐dependently inhibited by anpirtoline. In this respect, anpirtoline mimicked other 5‐HT 3 receptor antagonists; the rank order of potency was ondansetron>anpirtoline>metoclopramide. 4 The concentration‐response curve for 5‐HT as a stimulator of [ 14 C]‐guanidinium influx was shifted to the right by anpirtoline (apparent pA 2 : 7.78). 5 In urethane‐anaesthetized rats, anpirtoline 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 cisplatin in the domestic pig caused a consistent emetic response which was antagonized by anpirtoline. 7 It is concluded that anpirtoline, which was previously characterized as a 5‐HT 1 receptor agonist also proved to be a 5‐HT 3 receptor antagonist in several experimental models and, hence, exhibits a unique pattern of properties at different 5‐HT receptors.