Potter W Z, Calil H M, Manian A A, Zavadil A P, Goodwin F K
Biol Psychiatry. 1979 Aug;14(4):601-13.
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.
研究三环类抗抑郁药血浆浓度与临床反应之间可能存在的关系时，仅测定了这些药物的叔胺和仲胺形式。本研究表明，三环类抗抑郁药的羟基代谢产物可能也具有活性。羟基化的丙咪嗪、地昔帕明、氯米帕明和去甲替林对去甲肾上腺素和5-羟色胺摄入突触体的抑制作用与其母体化合物相同。羟基化的去甲替林和丙咪嗪可逆转或预防利血平引起的运动迟缓及眼睑下垂。长期服用丙咪嗪后，大鼠包括脑脊液在内的组织中会出现显著的稳态浓度的未结合羟基化代谢产物。考虑到人体中三环类抗抑郁药羟基化代谢产物的稳态浓度，可能有助于阐明活性药物浓度与临床疗效之间是否存在关系。
