Para-hydroxytranylcypromine: presence in rat brain and heart following administration of tranylcypromine and an N-cyanoethyl analogue.
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 of p-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 degrees C until time of analysis. Tissue levels of p-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 of p-OHTCP were present in both brain and heart after TCP and CE-TCP administration. Higher levels of p-OHTCP were present in the brain than in the heart after TCP treatment, but this situation was reversed with the CE-TCP-treated rats. Since p-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.
Nazarali
A J
AJ
PMHAC Research Unit, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Baker
G B
GB
Coutts
R T
RT
Greenshaw
A J
AJ
D000818:Animals; D001923:Brain Chemistry; D002849:Chromatography, Gas; D006207:Half-Life; D007202:Indicators and Reagents; D007274:Injections, Intraperitoneal; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014191:Tranylcypromine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics
D007202:Indicators and Reagents; C049286:4-hydroxytranylcypromine; D014191:Tranylcypromine; C044652:N-2-cyanoethyltranylcypromine