Effect of desipramine, phenoxybenzamine and yohimbine on beta-adrenoceptors and cyclic AMP production in the rat brain

Abstract

In rat brain, the number of beta-adrenoceptors and activity of noradrenaline-dependent adenylate cyclase were examined after treatment with desipramine (7.5 mg kg-1 day-1) for three days alone or in combination with the alpha 2-adrenoceptor antagonist, yohimbine (2 mg kg-1 12 hr-1), or with phenoxybenzamine (7.5 mg kg-1 day-1), which is a more potent inhibitor of alpha 1 than alpha 2-adrenoceptors. The only treatment which significantly decreased the specific binding of the beta-adrenoceptor antagonist, [3H]dihydroalprenolol was the combination of desipramine with yohimbine. Desipramine alone and desipramine with yohimbine also significantly reduced the formation of cyclic AMP in response to incubation with noradrenaline, the response to the drug combination being accounted for by addition of the individual effects of the drugs. The results showed that decreases in the activity of noradrenaline-dependent adenylate cyclase could become apparent before decreases in beta-adrenoceptor numbers. Whether these rapid changes in noradrenaline-dependent adenylate cyclase or in numbers of beta-adrenoceptors which are produced by combination of desipramine with an alpha 2-adrenoceptor antagonist, are of therapeutic value remains to be elucidated.