Reduction of responses to angiotensin II by antidepressant drugs.
The effects of the antidepressant drugs desipramine, fluoxetine and tranylcypromine and the non-antidepressant control cocaine on angiotensin II function were determined in vivo by use of angiotensin-induced drinking in rats and in vitro using contractile responses of the rat uterus. The results of the drinking studies showed that the three antidepressants, but not cocaine, reduced the dipsogenic effects of angiotensin II. In vitro, all of the drugs reduced the effects of not only angiotensin but also acetylcholine and oxytocin on the uterus. The inhibition appeared to be non-competitive in all cases. These results indicate that the antidepressant drugs reduced the activity of angiotensin II, albeit non-selectively, and suggest that the previously reported effects of antidepressants on isoprenaline-induced drinking in rats reflect an action on angiotensin activity rather than a reduction of beta-adrenoceptor activity as previously suggested.
Gard
P R
PR
Department of Pharmacy, University of Brighton, Moulsecoomb, UK.
Mandy
A
A
Whiting
J M
JM
Nickels
D P
DP
Meakin
A J
AJ
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects*; D004347:Drug Interactions; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010121:Oxytocin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014191:Tranylcypromine / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects
D000928:Antidepressive Agents; D005473:Fluoxetine; D000804:Angiotensin II; D014191:Tranylcypromine; D010121:Oxytocin; D003042:Cocaine; D007545:Isoproterenol; D000109:Acetylcholine; D003891:Desipramine