Pharmacologic evidence that high dose chronic amitriptyline and desipramine down-regulate alpha 2-receptor-mediated hypothermia in the rat.
The effects of a three week course of treatment of amitriptyline (AMI) and desipramine (DMI) (3.2 and 10 mg/kg, s.c., b.i.d.) were studied on the hypothermic response to clonidine (0.1 mg/kg, s.c.) in male adult albino rats. Single doses of clonidine in normal unmedicated rats produced a marked (about 2 degrees C) fall in body temperature. In contrast, 0.9% NaCl control injections had no significant effect. The clonidine-induced hypothermia was prevented by yohimbine pretreatment (3.2 mg/kg, i.p., 1/2 hr before), suggesting an alpha 2-mediated response. On days 8 and 14 of chronic tricyclic antidepressant (TCA) treatment, the hypothermic response was prolonged. Four days after the abrupt withdrawal of 20 days of TCA treatment (10 mg/kg, s.c., b.i.d.), the clonidine-induced hypothermia response was attenuated consistent with down-regulation of alpha 2-receptors. This latter effect was not observed with a dose of 3.2 mg/kg, s.c., b.i.d. of either TCA.
D000639:Amitriptyline / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000097:blood / Q000494:pharmacology*; D006207:Half-Life; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D000639:Amitriptyline; D015016:Yohimbine; D003000:Clonidine; D003891:Desipramine