Flerobuterol: a potential antidepressant drug related to beta-adrenergic agonists. Experimental profile in mice.
The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.
Centre de recherches du laboratoire L Lafon, Maisons-Alfort, France.
J
J
Duteil
F A
FA
Rambert
A M
AM
Pointeau
P
P
Mangiameli
E
E
Assous
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D004347:Drug Interactions; D007035:Hypothermia / Q000139:chemically induced; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010095:Oxotremorine / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D015016:Yohimbine / Q000633:toxicity
D000318:Adrenergic beta-Agonists; D000928:Antidepressive Agents; D015016:Yohimbine; D010095:Oxotremorine; D012110:Reserpine; C071321:flerobuterol; D001058:Apomorphine; D007099:Imipramine; D000420:Albuterol