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

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.