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

J Simiand, PE Keane, J Guitard, X Langlois… - European journal of …, 1992 - Elsevier
J Simiand, PE Keane, J Guitard, X Langlois, N Gonalons, P Martin, A Bianchetti, G Le Fur…
European journal of pharmacology, 1992Elsevier
Abstract β 2-Adrenoceptor agonists possess antidepressant-like activity in animals and man,
but their peripheral side-effects prevent their therapeutic use. Atypical β-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 β-adrenoceptor agonist, SR 58611A. SR 58611A was active with
minimal effective doses of 0.1–0.3 mg kg− 1 ip in several models (antagonism of the …
Abstract
β2-Adrenoceptor agonists possess antidepressant-like activity in animals and man, but their peripheral side-effects prevent their therapeutic use. Atypical β-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 β-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 hypothemia induced by apomorphine and reserpine; potentiation of the toxicity produced by yohimbine; reversal of learned helplessness), but was inactive in the test reserpine-induced ptosis and behavioural despair. The antidepressant-like effect of SR 58611A was not antagonised by selective β1- or β2-adrenoceptor antogonist, but was blocked by high doses of the non-selective β-adrenoceptor antagonists, propranolol and alprenolol. Unlike β2-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.
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