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  • Title: Hydroxylated metabolites of tricyclic antidepressants: preclinical assessment of activity.
    Author: Potter WZ, Calil HM, Manian AA, Zavadil AP, Goodwin FK.
    Journal: Biol Psychiatry; 1979 Aug; 14(4):601-13. PubMed ID: 486616.
    Abstract:
    Studies investigating a possible relationship between the plasma concentration of tricyclic antidepressants and clinical response have measured only the tertiary and secondary amine forms of these drugs. The present study shows that the hydroxy metabolites of tricyclic antidepressants might also be active. Hydroxylated imipramine, desipramine, chlorimipramine, and nortriptyline inhibit the uptake of norepinephrine and serotonin into synaptosomes to the same extent as do their parent compounds. Hydroxylated nortriptyline and imipramine reverse or prevent reserpine-induced motor retardation and ptosis. Following chronic imipramine, significant steady-state concentrations of unconjugated hydroxylated metabolites are present in rat tissues including the cerebrospinal fluid. Accounting for steady-state concentrations of hydroxylated metabolites of tricyclic antidepressants in man may help to clarify whether there is a relationship between active drug concentration and clinical effect.
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