BRL 24924: a potent agonist at a non-classical 5-HT receptor positively coupled with adenylate cyclase in colliculi neurons

Eur J Pharmacol. 1989 Mar 21;162(2):381-4. doi: 10.1016/0014-2999(89)90304-x.

Abstract

A non-classical 5-hydroxytryptamine (5-HT) receptor that we have previously proposed to call 5-HT4 and which mediates stimulation of adenylate cyclase activity in mouse embryo colliculi neurons in primary culture was also stimulated by substituted benzamide derivatives such as metoclopramide and BRL 24924 ([ (+/-)-(endo)]-4-amino-5-chloro-2-methoxy-N-(1-azabicyclo-[3.3.1]-non- 4-yl)-benzamide hydrochloride). The non-additivity of the effects of 5-HT and BRL 24924 on cAMP formation and the inhibition by ICS 205 930, a potent 5-HT3 antagonist, suggest that 5-HT and BRL 24924 act on the same receptor. In light of these results, we think that a similarity may exist between the non-classical 5-HT receptor, coupled with an adenylate cyclase in colliculi neurons, and the non-classical 5-HT receptor, involved in gastric and ileum motility which is specifically stimulated by substituted benzamide derivatives in the same order of potency (metoclopramide, BRL 24924).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • Benzamides / pharmacology*
  • Bridged Bicyclo Compounds / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Bridged-Ring Compounds / pharmacology*
  • Cyclic AMP / biosynthesis
  • Embryo, Mammalian
  • Female
  • Indoles / pharmacology
  • Metoclopramide / pharmacology
  • Mice
  • Neurons / drug effects
  • Neurons / enzymology*
  • Pregnancy
  • Serotonin Antagonists* / pharmacology
  • Tropisetron

Substances

  • Benzamides
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Bridged-Ring Compounds
  • Indoles
  • Serotonin Antagonists
  • Tropisetron
  • renzapride
  • Cyclic AMP
  • Adenylyl Cyclases
  • Metoclopramide