Acceleration of β-receptor desensitization in combined administration of antidepressants and phenoxybenzamine

Fulton T. Crews, Steven M. Paul, Frederick K. Goodwin

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


The delayed therapeutic effects of antidepressants (usually between 10 and 14 days)1,2 and of the tricyclic antidepressants in particular, are believed (on the basis of animal experiments3-8) to lie in a progressive decrease of the sensitivity of cortical β-adrenergic receptors. This is thought to be due to an increase in the synaptic concentration of noradrenaline, in turn accomplished by a decrease in the sensitivity of the presynaptic α2 receptors which normally regulate noradrenaline secretion by a negative feedback mechanism. This model suggests that the desensitization of postsynaptic β-receptors by antidepressants should be accelerated by the inhibition of the presynaptic α2-adrenergic system, and we have indeed observed such an effect in preliminary studies with desipramine and phenoxybenzamine (PBZ) combined9. We now show that the administration of either tricyclic or monoamine oxidase inhibitor antidepressants in combination with PBZ, an irreversible α-adrenergic blocker9,10, accelerates and intensifies the desensitization of β-adrenergic receptors. Our observations may have therapeutic implications.

Original languageEnglish
Pages (from-to)787-789
Number of pages3
Issue number5809
StatePublished - 1981


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