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Tyramine‐induced noradrenaline release from rat brain slices: prevention by (‐)‐deprenyl
Author(s) -
Glover Vivette,
Pycock C.J.,
Sandler M.
Publication year - 1983
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1983.tb11059.x
Subject(s) - clorgyline , monoamine oxidase , tyramine , chemistry , pharmacology , monoamine oxidase b , selegiline , phenelzine , catecholamine , endocrinology , medicine , enzyme , biochemistry , biology , disease , parkinson's disease
1 Clorgyline (1 and 10 μ M ) and (+)‐deprenyl (10 μ M ) both significantly potentiated the tyramine (100 μ M )‐induced release of [ 3 H]‐noradrenaline from rat cerebral cortex slices. (‐)‐Deprenyl (50 μ M ) significantly reduced it, while lower concentrations had no effect on noradrenaline release. However, in combination, 1 μ M (‐)‐deprenyl blocked the release‐facilitating action of 1 μ M clorgyline, and 10 μ M (‐)‐deprenyl that of 10 μ M (+)‐deprenyl. 2 Low concentrations of (+)‐ and (‐)‐deprenyl (1 and 10 μ M ), both selectively inhibited phenylethylamine oxidation by monoamine oxidase B. Higher concentrations of (‐)‐deprenyl (20 and 50 μ M ) also inhibited 5‐hydroxytryptamine oxidation by monoamine oxidase A. Clorgyline (1 and 10 μ M ) 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. 3 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.