[3H]Zacopride: Ligand for the Identification of 5-HT3 Recognition Sites

Abstract

[³H]Zacopride displayed saturable binding to homogenates of the rat entorhinal cortex as measured by the inclusion of the 5-HT₃ receptor antagonist BRL 43694 in the incubation media. Scatchard analysis indicated a single high affinity binding site (K_D 0.76 ± 0.08 nM, B_max 77.5 ±6.5 fmol (mg protein)⁻¹) with a Hill slope close to unity. Other 5-HT₃ receptor antagonists (zacopride, ICS 205–930, GR38032F, GR65630, metoclopramide and cocaine) also competed for the binding site displacing 60% of the total [³H]zacopride binding. 5-HT and 2-methyl-5-HT also were competitive antagonists for [³H]zacopride binding whereas 5-HT₁/5-HT₂ agonists and antagonists, and agents acting on other neurotransmitter receptors had K_i values greater than 10⁻⁵ M. It is concluded that [³H]zacopride may prove a useful ligand for the study of 5-HT₃ recognition sites.