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.
Département de Pharmacologie, Faculté de Médecine La Pitié-Salpetrière, Paris, France.
J
J
Simiand
P E
PE
Keane
J
J
Guitard
X
X
Langlois
N
N
Gonalons
P
P
Martin
A
A
Bianchetti
G
G
Le Fur
P
P
Soubrié
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002976:Clenbuterol / Q000494:pharmacology; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D011943:Receptors, Adrenergic, beta; D013764:Tetrahydronaphthalenes; D000526:Alprenolol; D011433:Propranolol; D007099:Imipramine; C076252:amibegron; D000420:Albuterol; D002976:Clenbuterol