Tranylcypromine (‘Parnate’) overdose: measurement of tranylcypromine concentrations and MAO inhibitory activity and identification of amphetamines in plasma

Abstract

SynopsisA case of tranylcypromine overdose is reported. Tranylcypromine, amphetamine, methamphetamine and phenylethylamine were detected in the plasma by gas chromatography and their identity confirmed by mass spectrometry. The data suggested that the amphetamines were metabolic products of tranylcypromine. Platelet monoamine oxidase activity was more than 95% inhibited during the 72 h after the overdose despite complete clinical recovery by that time. The possible role of amphetamines and phenylethylamine in causing the clinical manifestations of tranylcypromine overdose is discussed.

Tranylcypromine, but not moclobemide, prolongs the inhibitory action of dopamine on midbrain dopaminergic neurons: An in vitro electrophysiological study

“…In fact, amphetamine, by increasing the release of dopamine in the slice, inhibits the spontaneous firing of DA cells. Thus, the effect of tranylcypromine on the DA signal appears to be mainly dependent on the in vitro blockade of MAO (Katz et al, 1981;Youdim et al, 1979) and not on a direct influence of this MAOI on the DA transporter. …”

Measuring Endogenous 5-HT Release by Emission Tomography: Promises and Pitfalls

“…Mixed pharmacology of the compound or its metabolites may cause particular problems especially if high doses are required. For example, the potential for interaction of clomipramine with 5-HT 1A and 5-HT 2A receptors (Hyttel, 1994), norfenfluramine with 5-HT 2A receptors (Rothman and Baumann, 2002) and amphetamine, a proposed metabolite of tranylcypromine, with SERT (Sherry et al, 2000;Youdim et al, 1979) could have implications for certain challenges. The assumption that a direct effect of the releasing agent on the target receptor is unlikely because of 'low affinity' cannot be relied upon, unless the actual brain concentration of these compounds and their metabolites is measured.…”

Discrimination Between Drug Abuse and Medical Therapy: Case report of a tranylcypromine overdose-related fatality

“…11 However, there are conflicting reports as to whether tranylcypromine is metabolised to amphetamine and methamphetamine. 3,4,8,12,13 In the current case, tranylcypromine was detected in combination with amphetamine and methamphetamine in the urine sample of a fatal overdose case. One possible explanation for the presence of amphetamines in such postmortem specimens is the biotransformation of tranylcypromine to amphetamine and methamphetamine within the human body.…”

“…1,3 This metabolic formation of amphetamine is responsible for the therapeutic effects of tranylcypromine as well as those that occur following withdrawal. [1][2][3][4] A therapeutic dose of tranylcypromine constitutes 30 mg per day, usually given in divided doses. While this amount of the drug is unlikely to produce a marked degree of amphetamine-like central activity, the e214 | SQU Medical Journal, May 2017, Volume 17, Issue 2 were analysed quantitatively to detect ethanol and methanol via headspace gas chromatography using the 6890N Network Gas Chromatograph (Agilent Technologies Inc.) equipped with a flame ionisation detector.…”