N-CHLOROMETHYL QUINUCLIDINIUM DERIVATIVES - A NEW CLASS OF IRREVERSIBLE LIGANDS FOR 5-HT3 RECEPTORS

The quinuclidine ring of potent 5-HT3 receptor antagonists such os zac opride and the 1,8-naphthalimide derivatives 3 reacts with methylene c hloride at room temperature to produce the corresponding chloromethyl quaternary derivatives. The compounds derived from (S)-zacopride and ( R)-3 are potent ligands for 5-HT3 receptor as evaluated in binding ass ays. incubated with entorhinal cortex membranes, they produced a dose- dependent decrease in the B-max value for [H-3]-BRL-43694 which was in hibited by zacopride or GR 38032F. The quaternary derivative of (R)-3 is a promising tool for studying 5-HT3 receptors due to its high affin ity and fluorescent properties.