NAChR agonists/antagonists

Tropisetron [ICS-205,930, Novoban, (172) in Fig. 14.18 Novartis] is a potent 5-HT, receptor antagonist = 0.38-3.1 nM) (483-485)that has recently been found to possess a, nAChR subtype antagonist activity (437) (see Table 14.13) and a, nAChR partial agonist activity (445). In rat behavioral studies, tropisetron attenuated scopolamine-induced memory deficits in the passive-avoidance test (438), and spatial navigation deficits in the Morris water-maze task (463), and improved the retention of a conditioned response in rats with p-chloroamphetamine-induced deficits (486). Tropisetron is currently marketed for the treatment of nausea and vomiting associated with chemotherapy treatments (485). 

M) and mecamylamine (lO M) were also tested as nAChR agonist and antagonist, respectively. 

Concentration-effect curve of an antagonist ( , d-tubocurarine + agonist) and agonist alone ( , suberyldicho-line) at Torpedo nAChR expressed in oocytes (unpublished observations)... 

Tropisetron (a selective 5-HT3R antagonist, Fig. 1) has been found to be also a potent and selective but partial agonist of a7-nAChR thus potentially effecting learning and memory processes [39], Clinical implications and use are still not elaborated. 

Tropisetron is a synthetic TTA containing an esterified tropine moiety (Fig. 1). This drug is a potent antiemetic selective 5-HT3 receptor antagonist to treat postoperative and chemotherapy-induced vomiting and nausea by daily intravenous or oral administration [70], Furthermore, tropisetron is a potent and selective partial agonist of a7-nAChR [39],... 

---