Summary
para-Hydroxytranylcypromine (p-OHTCP) has recently been unequivocally identified in our laboratory as a metabolite of the antidepressant tranylcypromine (TCP). In the study reported here, we have determined brain and heart levels ofp-OHTCP in the rat after intraperitoneal administration of a 0.1 mmol/kg dose of TCP or N-(2-cyanoethyl)tranylcypromine (CE-TCP). The animals were killed at 5, 15, 30, 60, 120 or 240 min after drug administration and the tissues (brain and heart) rapidly dissected out. The tissues were frozen in isopentane on solid carbon dioxide and stored at −20°C until time of analysis. Tissue levels ofp-OHTCP, TCP and CE-TCP were determined after aqueous pentafluorobenzoylation by conducting analyses with a gas-liquid chromatograph equipped with a fused silica (SE-54) capillary column and an electron-capture detector. Our results show that substantial concentrations ofp-OHTCP were present in both brain and heart after TCP and CE-TCP administration. Higher levels ofp-OHTCP were present in the brain than in the heart after TCP treatment, but this situation was reversed with the CE-TCP-treated rats. Sincep-OHTCP has been shown to retain some MAO-inhibiting properties and to have effects on uptake of catecholamines and serotonin it could therefore contribute to the pharmacological profile of TCP.
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Funding was provided by the Provincial Mental Health Advisory Council (PMHAC) and by the Alberta Heritage Foundation for Medical Research.
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Nazarali, A.J., Baker, G.B., Coutts, R.T. et al. Para-hydroxytranylcypromine: presence in rat brain and heart following administration of tranylcypromine and an N-cyanoethyl analogue. European Journal of Drug Metabolism and Pharmacokinetics 12, 207–214 (1987). https://doi.org/10.1007/BF03189899
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DOI: https://doi.org/10.1007/BF03189899