Desipramine and nortriptyline antagonize apomorphine and reserpine hypothermia by a different mechanism.
The reversal of hypothermia, induced by reserpine or by a high (16 mg) dose of apomorphine, in male Swiss mice, does not seem to utilize a common mechanism. Desipramine (20 mg kg-1 i.p., 60 min) or nortriptyline (8 mg kg-1 i.p., 60 min) increased temperature in both reserpine (2.5 mg kg-1 s.c., 18-19 h) and apomorphine (16 mg kg-1 s.c., 30 min) treated mice. In apomorphine-treated animals the effect of both drugs was reversed by the mixed dopaminergic D1- D2-antagonist haloperidol (1 mg kg-1 i.p., 90 min), the D1-receptor blocking drug SCH 23390 (0.05 mg kg-1 s.c., 30 min), the alpha 1-adrenoceptor blocking drugs prazosin (3 mg kg-1 s.c., 90 min) and phenoxybenzamine (20 mg kg-1 i.p., 65 min), the beta-adrenoceptor blocking drug (+/-)-propranolol (10 mg kg-1 i.p., 120 min), and the opioid antagonist naloxone (2 mg kg-1 i.p., 15 min). In contrast the selective D2-antagonist (+/-)-sulpiride (100 mg kg-1 i.p., 90 min), and the alpha 2-antagonist yohimbine (2 mg kg-1 i.p., 75 min), failed to effect the reversal of apomorphine hypothermia brought about by desipramine or nortriptyline. Their temperature effects in reserpinized mice were not modified by any of the antagonists tested.
Volterra
G
G
A. Menarini Farmaceutici s.r.l., Pharmacological Research Division, Florence, Italy.
Borsini
F
F
Lecci
A
A
Meli
A
A
D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D001831:Body Temperature / Q000187:drug effects; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009661:Nortriptyline / Q000008:administration & dosage / Q000494:pharmacology*; D012110:Reserpine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*
D012110:Reserpine; D009661:Nortriptyline; D006220:Haloperidol; D001058:Apomorphine; D003891:Desipramine