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Recently, it has been suggested that antidepressant drugs exert their pharmacological action through functional changes in the adrenergic-receptor coupled adenylate cyclase system. In the present research, we examined the direct effects of antidepressants on adenylate cyclase (A-cyclase) activity by in vitro incubation of cell membranes from the cerebral cortex of rats with these drugs. All antidepressants examined, such as imipramine, clomipramine, amitriptyline, desipramine, mianserin and zimelidine inhibited A-cyclase in a dose dependent manner. Antidepressants did not exert any influence on Mn2+-induced elevation of A-cyclase, but significantly suppressed F(-)-stimulated A-cyclase activity. GTP-induced elevation of A-cyclase was completely inhibited by prior incubation with antidepressants. Our conclusion, therefore, is that antidepressants may reduce A-cyclase activity not by inhibiting the function of the catalytic unit of A-cyclase, but by suppressing the N-protein function.
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