The effects of tranylcypromine isomers on norepinephrine-H3 metabolism in rat brain

Abstract

The effects of d- and l-tranylcypromine on the disposition and metabolism of intracisternally administered l-norepinephrine-H3 were studied in rat brain. Both isomers inhibited the deamination of norepinephrine-H3. However, d-tranylcypromine was considerably more potent than the l-isomer in this respect. In addition, the l-isomer of tranylcypromine was found to enhance the disappearance of endogenous and tritiated norepinephrine from brain. Although this action appeared to result from an increase in catecholamine release, the possibility of uptake inhibition could not be eliminated. The l-isomer of tranylcypromine enhanced the disappearance of norepinephrine-H3 from brain when administered both 20 and 90 min following intracisternal injection of the label. Comparable doses of d-tranylcypromine did not exhibit this effect. Larger increases in brain levels of normetanephrine-H3 were produced by d,l-tranylcypromine than by either the d- or l-isomer alone, indicating that the racemic mixture may produce the greatest increase in the interaction of norepinephrine with its postsynaptic receptors.

4‐fluorotranylcypromine, a novel monoamine oxidase inhibitor: Neurochemical effects in rat brain after short‐ and long‐term administration

“…Results are expressed as percent inhibition of control (vehicle-treated) MAO-A activity (n = 4-8). TCP, which is structurally similar to amphetamine, has been reported to have effects on the uptake and release of catecholamines in brain tissue [Hendley and Snyder, 1968;Schildkraut, 1970;Baker et al, 1980Baker et al, , 1992Reigle et al, 1980], and it has been suggested that such actions may contribute to the antidepressant action [Hendley and Snyder, 1968;Reigle et al, 1980] and/or some of the cardiovascular side effects associated with TCP [Mallinger et al, 1986;Keck et al, 1991]. All values are significantly different from control values.…”

Role of monoamines in behavior of reserpinized rats given tranylcypromine stereoisomers

“…While racemic tranylcypromine is known to counteract behavioral effects of reserpine (Tedeschi, Tedeschi, Ames, Cook, Mattis, and Fellows, 1959), the present findings show reserpine-reversal to depend on pharmacological actions present in the (+)-isomer but absent in the (--)-isomer. Tranylcypromine stereoisomers have stereoselective effects on monoamine oxidase inhibition, monoamine uptake mechanisms and catecholamine release (Zirkle, Kaiser, Tedeschi, and Tedeschi, 1962;Horn and Snyder, 1972;Tuomisto, 1978;Reigle, Orsulak, Avni, Platz, and Schildkraut, 1980;Reynolds, Riederer, and Rausch, 1980), but it is unknown whether these actions can account fully for their stereoselective effects in reserpinized rats. Perhaps further studies on stereoselective pharmacological effects of tranylcypromine stereoisomers can clarify the molecular basis of reserpine-induced depression and of its reversal by psychoactive drugs.…”

“…Tranylcypromine stereoisomers [(+)-and (--)-trans-2-phenylcyclopropylamine] have stereoselective actions on monoaminergic mechanisms; the (+)-isomer [(+)-TCP] appears to influence mainly tryptaminergic mechanisms in addition to inhibition of monoamine oxidase, while the (--)-isomer [(--)-TCP] seems to act primarily on catecholaminergic mechanisms as an indirect agonist (see Smith, 1980;Reigle, Orsulak, Avni, Platz, and Schildkraut, 1980). The present study was carried out to investigate further the actions of tranylcypromine stereoisomers on monoaminergic neurotransmission using reserpine-reversal as the behavioral test.…”

Direct separation of tranylcypromine enantiomers and their profile in an atypical depressive patient

“…Previous studies have shown that the TCP enantiomers have markedly different pharmacological properties. (+)-R-TCP is a more effective M A 0 inhibitor, while ( -)-S-TCP is a better inhibitor of noradrenaline and dopamine uptake (Horn and Snyder, 1972;Fuentes et ul., 1976;Reigle et al, 1980;Reynolds et al, 1980;Hampson et al, 1986;Tuomisto and Smith, 1986). (+)-R-TCP has also been shown to increase levels of brain 5-hydroxytryptamine over those caused by the (-)-S-enantiomer (Smith and Peterson, 1982).…”