121650-80-4

Pancopride is a new potent and selective 5-HT ₃ receptor antagonist, orally and parenterally effective against cytotoxic drug-induced emesis. Pancopride displayed high affinity (K _i =0.40 nM) for [ ³ H]GR65630-labelled 5-HT ₃ recognition sites in membranes from the cortex of rat brains.

Pancopride antagonizes 5-HT-induced bradycardia in anaesthetized rats when administered i.v. 5 min (ID ₅₀ =0.56 μg/kg) or p.o. 60 min (ID ₅₀ =8.7 μg/kg) before 5-HT challenge. A single oral dose (10 μg/kg) of Pancopride produced a significant inhibition of the bradycardic reflex over an 8-h period. Pancopride dose dependently inhibited the number of vomiting episodes and delayed the onset of vomiting induced by cisplatin in dogs (ID ₅₀ =3.6 μg/kg i.v. and 7.1 μg/kg p.o.). Pancopride inhibits vomiting induced by cisplatin in dogs and is also effective in blocking mechloretamine- and dacarbazine-induced emesis lacking any antidopaminergic activity. Pancopride stimulates gastric emptying of glass beads in the rat (DE ₅₀ =0.032 mg/kg p.o.). Pancopride (1 mg/kg i.p.) also reverses cisplatin induced slowing of gastric emptying in the rat.