Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action.
The relative potencies of a variety of neuroleptic drugs and antidepressant agents in competing for the binding of 3H-clonidine and 3H-yohimbine to alpha 2-adrenergic receptors of the rat cerebral cortex were quantified. The rank order of potencies of neuroleptics tested in competing for both ligand bindings is: clocapramine, carpipramine much greater than perphenazine, fluphenazine, alpha,beta-flupentixol greater than propericiazine, levomepromazine greater than chlorpromazine, pimozide greater than moperone much greater than haloperidol, sulpiride. Among the antidepressants, mianserin is the most potent antidepressant. Amitriptyline has a substantial affinity, while desipramine, imipramine, and clomipramine are the least potent. It is concluded that a number of neuroleptics and antidepressant agents display a potent or moderate affinity to alpha 2-receptor sites. These findings support the suggestion that some neuroleptics enhance the release of norepinephrine (NE) mainly by acting on presynaptic alpha 2-receptors, and that the alpha 2-receptor blocking property may have an important role in the mechanism of the antidepressant effect of some neuroleptic compounds.
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000378:metabolism*; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects*; D003000:Clonidine / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003000:Clonidine