Chronic tranylcypromine treatment induces functional alpha 2-adrenoceptor down-regulation in rats.
The effects of chronic (28 d Alzet 2002 osmotic mini-pumps) administration of antidepressant drugs on the functional sensitivity of alpha 2-adrenoceptors and on monoamine oxidase activity has been assessed. Tranylcypromine, 4-fluorotranylcypromine and clorgyline (0.5-1.0 mg kg-1) induced a decrease in the motor-suppressant effects of clonidine (50 micrograms kg-1) observed at 9-10 and 23-24 days of drug administration. These effects were associated with marked decreases in type A (clorgyline) or type A and B monoamine oxidase activity (tranylcypromine and 4-fluorotranylcypromine). The results indicate that alpha 2-adrenoceptor down-regulation is an early emergent feature of adaptive changes in noradrenaline systems induced by prolonged exposure to tranylcypromine.
Greenshaw
A J
AJ
Department of Psychiatry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Nazarali
A J
AJ
Rao
T S
TS
Baker
G B
GB
Coutts
R T
RT
D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D008297:Male; D008995:Monoamine Oxidase / Q000032:analysis; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects*; D014191:Tranylcypromine / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D014191:Tranylcypromine; D008995:Monoamine Oxidase; D003010:Clorgyline