Tyramine-induced noradrenaline release from rat brain slices: prevention by (-)-deprenyl.
Clorgyline (1 and 10 microM) and (+)-deprenyl (10 microM) both significantly potentiated the tyramine (100 microM)-induced release of [3H]-noradrenaline from rat cerebral cortex slices. (-)-Deprenyl (50 microM) significantly reduced it, while lower concentrations had no effect on noradrenaline release. However, in combination, 1 microM (-)-deprenyl blocked the release-facilitating action of 1 microM clorgyline, and 10 microM (-)-deprenyl that of 10 microM (+)-deprenyl. Low concentrations of (+)- and (-)-deprenyl (1 and 10 microM), both selectively inhibited phenylethylamine oxidation by monoamine oxidase B. Higher concentrations of (-)-deprenyl (20 and 50 microM) also inhibited 5-hydroxytryptamine oxidation by monoamine oxidase A. Clorgyline (1 and 10 microM) inhibited both enzymes. Thus, the effects of these drugs on noradrenaline-release cannot be explained solely in terms of irreversible inhibition of monoamine oxidase A and B, and other possible mechanisms are discussed. If the brain-slice model faithfully mirrors the sequence of events manifesting peripherally as the tyramine hypertensive response ('cheese effect'), then it is possible that low doses of (-)-deprenyl, administered with antidepressant monoamine oxidase inhibitors, can prevent this adverse reaction.
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003010:Clorgyline / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D012642:Selegiline / Q000494:pharmacology*; D013237:Stereoisomerism; D014316:Tritium; D014439:Tyramine / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D014316:Tritium; D012642:Selegiline; D003010:Clorgyline; D009638:Norepinephrine; D014439:Tyramine