The pharmacology of B-type selective monoamine oxidase inhibitors; milestones in (-)-deprenyl research.
(-)-deprenyl cannot be considered as a simple, selective inhibitor of MAO-B. It increases the dopaminergic tone in the central nervous system by a complex mechanism. The MAO-B inhibition could result in a potentiation of the effect and the reduction of the dose of L-dopa, including the restoration of the sensitivity to L-dopa treatment, when the response to the drug has already been diminished or lost. Pre-treatment with (-)-deprenyl prevent the effect of neurotoxins like MPTP, 6-hydroxydopamine, DSP-4, AF64A by inhibiting the conversion of the pretoxin to toxin, or by inhibiting the neuronal reuptake mechanisms, or the combination of the two processes. However, other effects of the inhibitor cannot be ruled out. (-)-deprenyl, but not its (+)-enantiomer, proved to be a potent inhibitor of programmed cell death (apoptosis) of PC12 cells and that of human melanoma cells, in a concentration which does not induce MAO-B inhibition. The activity of MAO-B increases with age and the age related changes led to an overproduction of neurotoxic agents. The inhibition of the enzyme activity can play a preventive role against neurodegenerative brain disorders. The most widely used MAO-B inhibitor in the therapy is (-)-deprenyl and it lacks the "cheese reaction". The complex mechanism for the lack of the former effect is not fully known.
Magyar
K
K
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
Szende
B
B
Lengyel
J
J
Tekes
K
K
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007980:Levodopa / Q000627:therapeutic use; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D016716:PC12 Cells / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D012642:Selegiline / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D009498:Neurotoxins; D012642:Selegiline; D007980:Levodopa; D004298:Dopamine; D009638:Norepinephrine