Protein Phosphorylation System in the Mechanism of Action of Antidepressants
Although antidepressants are currently in widespread use as psychotropic drugs, their precise mechanism of action has not yet been elucidated. The strong potency of antidepressants for inhibiting the reuptake of catecholamines into presynaptic nerve terminals was initially the basis for Schildkraut’s proposal of the monoaminergic hypothesis of affective disorders (Schildkraut 1965). This hypothesis should be extended or revised, as the inhibition of catecholamine reuptake is observed within minutes to hours after administration of a single antidepressant, whereas the clinical effect in depressive patients is often seen only after 1 to 3 weeks of daily treatment. Vetulani and Sulser (1975) proposed that this delay in the occurrence of the therapeutic action could be correlated with the development of noradrenergic subsensitivity of the cyclic adenosine monophosphate (cAMP) generating system in the brain after chronic, but not acute, treatment with tricyclic antidepressants and with some atypical antidepressants.
KeywordsAntidepressant Treatment cAMP Response Element Binding Microtubule Assembly Tubulin Dimer Chronic Antidepressant Treatment
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