Effect of chlorpromazine on plasma adenosine 3',5'-cyclic phosphate level.
A subcutaneous injection of chlorpromazine hydrochloride (CPZ) at a dose of 10 mg/kg caused an increase in the plasma cyclic AMP level in male mice. Propranolol (2 mg/kg) and hexamethonium (50 mg/kg) abolished the elevation of plasma cyclic AMP induced by CPZ. Phentolamine (5 mg/kg) could not inhibit the effect of CPZ. Adrenalectomy completely inhibited the elevation of plasma cyclic AMP produced by CPZ. Pretreatment with 6-hydroxydopamine (100 mg/kg, i.v., 24 hr before) failed to reduce the elevation of the plasma cyclic AMP level produced by CPZ. Intracere-broventricular administration of CPZ (5-25 microg/mouse) also increased plasma cyclic AMP levels. These findings indicate that CPZ activated the sympathetic nervous system by acting on the CNS, thereby increasing plasma cyclic AMP levels through the stimulation of beta-adrenoceptors mainly by catecholamines released from the adrenal medulla.
Nakadate
T
T
Department of Pharmacology, School of Medicine, Keio University, Shinanomachi, Shinjuku-ku, Tokyo 160, Japan.
Muraki
T
T
Tokunaga
Y
Y
Kato
R
R
D000315:Adrenalectomy; D000818:Animals; D002395:Catecholamines / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects; D002746:Chlorpromazine / Q000008:administration & dosage / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D051379:Mice; D016627:Oxidopamine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects
D002395:Catecholamines; D016627:Oxidopamine; D000242:Cyclic AMP; D002746:Chlorpromazine