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

Abstract

In rat brain, the number of β-adrenoceptors and activity of noradrenaline-dependent adenylate cyclase were examined after treatment with desipramine (7.5mg kg −1 day −1) for three days alone or in combination with the α 2-adrenoceptor antagonist, yohimbine (2 mg kg −1 12hr −1), or with phenoxybenzamine (7.5 mg kg −1day −1), which is a more potent inhibitor of α 1, than α 2-adrenoceptors. The only treatment which significantly decreased the specific binding of the β-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 β-adrenoceptor numbers. Whether these rapid changes in noradrenaline-dependent adenylate cyclase or in numbers of β-adrenoceptors which are produced by combination of desipramine with an α 2-adrenoceptor antagonist, are of therapeutic value remains to be elucidated.