Effects of some atypical antidepressants on beta-adrenoceptor binding and adenylate cyclase activity in the rat forebrain.
The effects of daily administration to rats of desipramine, talsupram, tomoxetine, maprotiline, nomifensine, mianserin and citalopram (each 10 mg kg-1 day-1) for 4 weeks on [3H]dihydroalprenolol ([3H]DHA) binding in the cerebral cortex and on the noradrenaline-sensitive adenylate cyclase in the limbic forebrain were determined. Of these compounds, desipramine was alone in reducing [3H]DHA binding and in attenuating the cAMP response. Two selective noradrenaline uptake inhibitors, talsupram and tomoxetine each reduced the cAMP response but without affecting [3H]DHA binding. The other drugs lacked effect on both measures indicating (except for citalopram) that reduction in sensitivity of beta-adrenoceptors and of the noradrenaline-sensitive cAMP response might not be a simple consequence of noradrenaline uptake inhibition. The lack of effect of citalopram on the sensitivity of the beta-adrenoceptor system suggests that antidepressants with selective 5-HT uptake inhibitory properties owe their antidepressant activity to other mechanisms.
Garcha
G
G
Smokcum
R W
RW
Stephenson
J D
JD
Weeramanthri
T B
TB
D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism
D000928:Antidepressive Agents; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D009638:Norepinephrine