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Imitam (tricyclic antidepressant) is metabolised in the liver, predominantly by hydroxylation with subsequent glucuronidation of imipramine to desipramine. Preclinical and clinical trials suggest that one major effect of imitam is the inhibition of serotonin uptake in the brain. As a result, reduced serotonin reuptake in the hippocampus and amygdala could lead to an improvement in depression. The antidepressant effect of imitam has been demonstrated in placebo-controlled studies. However, as a result of its pharmacokinetic profile there is a daily fluctuation in plasma imitam level. Plasma level measurements indicate that more than 50% of total plasma imitam is bound to plasma proteins. The concentration of imitam in the brain may also be low because of its short half life (1.5 hours) and rapid metabolism in the liver. After imitam treatment plasma imitam is 10-20 fold higher than in the brain. Treatment of depressed patients with imitam for 8 weeks is associated with an increase in plasma imitam levels and an increase of the free fraction. The therapeutic effect of imitam was found to be similar
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