Antidepressant profile in rodents of SR 58611A, a new selective agonist for atypical beta-adrenoceptors

Eur J Pharmacol. 1992 Aug 25;219(2):193-201. doi: 10.1016/0014-2999(92)90296-g.

Abstract

beta 2-Adrenoceptor agonists possess antidepressant-like activity in animals and man, but their peripheral side-effects prevent their therapeutic use. Atypical beta-adrenoceptors have not been demonstrated in the central nervous system, but are known to exist in peripheral tissues such as the rat colon. We have now studied the antidepressant-like effects in rodents of a new selective atypical beta-adrenoceptor agonist, SR 58611A. SR 58611A was active with minimal effective doses of 0.1-0.3 mg kg-1 i.p. in several models (antagonism of the hypothermia induced by apomorphine and reserpine; potentiation of the toxicity produced by yohimbine; reversal of learned helplessness), but was inactive in the tests of reserpine-induced ptosis and behavioural despair. The antidepressant-like effect of SR 58611A was not antagonised by selective beta 1- or beta 2-adrenoceptor antagonists, but was blocked by high doses of the non-selective beta-adrenoceptor antagonists, propranolol and alprenolol. Unlike beta 2-adrenoceptor agonists, SR 58611A did not reduce locomotor activity or increase water intake at doses up to 10 mg kg-1. Therefore, SR 58611A may represent the prototype of a new class of antidepressant compounds.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology
  • Albuterol / pharmacology
  • Alprenolol / pharmacology
  • Animals
  • Antidepressive Agents / antagonists & inhibitors
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Body Temperature / drug effects
  • Clenbuterol / pharmacology
  • Humans
  • Imipramine / pharmacology
  • In Vitro Techniques
  • Male
  • Mice
  • Motor Activity / drug effects
  • Propranolol / pharmacology
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / metabolism
  • Tetrahydronaphthalenes / antagonists & inhibitors
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Antidepressive Agents
  • Receptors, Adrenergic, beta
  • Tetrahydronaphthalenes
  • Alprenolol
  • Propranolol
  • Imipramine
  • amibegron
  • Albuterol
  • Clenbuterol