Alpha-adrenergic receptors mediate imipramine/alarm substance-induced reaction in rats.
The mechanism of adverse imipramine-induced reactions (jitteriness, convulsions) was investigated by precipitating such reactions in rats with three injections (IP) of imipramine (5-40 mg/kg) at 24, 5, and 1 h before testing, and comparing their occurrence with comparable treatments using specific noradrenergic and serotonergic reuptake inhibitors [nortriptyline (10 or 30 mg/kg, IP), citalopram (0.5-5.0 mg/kg, IP)]. This initial study indicated that these reactions were mediated by imipramine's noradrenergic effects. Subsequent combinations of imipramine and an alpha 2 agonist (clonidine, 5 mg/kg) and antagonist (yohimbine, 2 mg/kg), and a beta-adrenergic antagonist (propranolol, 2 or 5 mg/kg) (all administered IP 0.5 h after the last injection of imipramine) suggested imipramine's adverse effects were mediated by alpha 2 receptors. The possible involvement of the locus ceruleus in these effects was considered.
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Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201.
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000633:toxicity*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D009661:Nortriptyline / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D018079:Receptors, GABA / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D018341:Receptors, Adrenergic, alpha-2; D018079:Receptors, GABA; D015283:Citalopram; D015016:Yohimbine; D012701:Serotonin; D012110:Reserpine; D011433:Propranolol; D009661:Nortriptyline; D003000:Clonidine; D007099:Imipramine; D009638:Norepinephrine