RELATIONSHIP BETWEEN TYRAMINE POTENTIATION AND SELECTIVE INHIBITION OF MONOAMINE OXIDASE TYPES A AND B IN THE RAT VAS DEFERENS
J. P. M. Finberg, M. Tenne
Abstract
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J. P. M. Finberg, M. Tenne
Abstract
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1 The degree of selective monoamine oxidase (MAO) inhibition produced by (-)-deprenyl, clorgyline, LY51641 and tranylcypromine was examined in relation to modification of tyramine and noradrenaline contractile responses of the rat isolated vas deferens. 2 All inhibitors possessed reversible alpha-adrenoceptor blocking activity, determined against noradrenaline on the denervated vas deferens. For LY51641 and tranylcypromine, antagonism was competitive, with pA2 values of 6.17 and 5.16. 3 Clorgyline, LY51641 and (-)-deprenyl (10(-5) M) inhibited the tyramine response while present in the organ bath: LY51641, which was the most potent as an alpha-adrenoceptor blocker, produced this effect at 10(-6) M. Responses to tyramine and noradrenaline were potentiated on wishing out the inhibitors, but noradrenaline potentiation was seen only when tyramine had been present in the system. 4 Tranylcypromine (10(-6) M) potentiated responses to noradrenaline and tyramine while present in the organ bath. 5 Potentiation of tyramine responses by clorgyline and LY51641 occurred at 91% and 64% inhibition of MAO type A respectively, although full potentiation of the tyramine response was elicited only when substantial inhibition of both enzyme types occurred. Selective inhibition of MAO type B by 67% (with deprenyl) was not associated with tyramine potentiation.
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1 The degree of selective monoamine oxidase (MAO) inhibition produced by (-)-deprenyl, clorgyline, LY51641 and tranylcypromine was examined in relation to modification of tyramine and noradrenaline contractile responses of the rat isolated vas deferens. 2 All inhibitors possessed reversible alpha-adrenoceptor blocking activity, determined against noradrenaline on the denervated vas deferens. For LY51641 and tranylcypromine, antagonism was competitive, with pA2 values of 6.17 and 5.16. 3 Clorgyline, LY51641 and (-)-deprenyl (10(-5) M) inhibited the tyramine response while present in the organ bath: LY51641, which was the most potent as an alpha-adrenoceptor blocker, produced this effect at 10(-6) M. Responses to tyramine and noradrenaline were potentiated on wishing out the inhibitors, but noradrenaline potentiation was seen only when tyramine had been present in the system. 4 Tranylcypromine (10(-6) M) potentiated responses to noradrenaline and tyramine while present in the organ bath. 5 Potentiation of tyramine responses by clorgyline and LY51641 occurred at 91% and 64% inhibition of MAO type A respectively, although full potentiation of the tyramine response was elicited only when substantial inhibition of both enzyme types occurred. Selective inhibition of MAO type B by 67% (with deprenyl) was not associated with tyramine potentiation.
Key concepts: Clorgyline, Tyramine, Tranylcypromine, Vas deferens, Long-term potentiation, Monoamine oxidase, Pharmacology, Chemistry