N-(2-cyanoethyl)tranylcypromine, a potential prodrug of tranylcypromine: its disposition and interaction with catecholamine neurotransmitters in brain.
The disposition of the N-cyanoethyl analogue of tranylcypromine (TCP) and the TCP formed from it have been studied in the rat brain following intraperitoneal (ip) administration (0.1 mmol/kg) and the resultant data compared with those obtained following an equimolar dose of TCP. Brain concentrations of the neurotransmitter amines dopamine (DA) and noradrenaline (NA) have also been determined, as well as the percentage inhibition of monoamine oxidase (MAO) types A and B. Our results indicate that the N-cyanoethyl analogue may be a useful prodrug of TCP, providing lower but more sustained concentrations of TCP in brain. Brain levels of DA were increased in a similar pattern after CE-TCP or TCP. Brain levels of NA were decreased by TCP at most time intervals, while CE-TCP produced a much less pronounced effect. Both CE-TCP and TCP inhibited MAO-A and MAO-B, with maximum inhibition occurring 60 min after CE-TCP dosing and 30 min after dosing with TCP, times at which brain concentrations of CE-TCP and TCP were at the maximum.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006207:Half-Life; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D009638:Norepinephrine / Q000378:metabolism*; D011355:Prodrugs; D051381:Rats; D011919:Rats, Inbred Strains; D014191:Tranylcypromine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*
D008996:Monoamine Oxidase Inhibitors; D011355:Prodrugs; D014191:Tranylcypromine; C044652:N-2-cyanoethyltranylcypromine; D004298:Dopamine; D009638:Norepinephrine