Neurochemical and Neuroprotective Effects of Some Aliphatic Propargylamines: New Selective Nonamphetamine-Like Monoamine Oxidase B Inhibitors
| Autor: | Bruce A. Davis, David A. Durden, W. G. Nicklas, Peter H. Yu, I. Terleckyj, Alan A. Boulton, Alistair J. Barber |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Benzylamines Serotonin Monoamine Oxidase Inhibitors Monoamine oxidase Neurotoxins Hypothalamus Mice Inbred Strains Pharmacology Biochemistry Neuroprotection Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Catecholamines Neurochemical Oral administration Dopamine medicine Animals Amines Monoamine Oxidase MPTP Amphetamines Homovanillic acid Brain Pargyline chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Monoamine oxidase B Caudate Nucleus medicine.drug |
| Zdroj: | Journal of Neurochemistry. 62:697-704 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1046/j.1471-4159.1994.62020697.x |
| Popis: | Aliphatic N-propargylamines have recently been discovered to be highly potent, selective, and irreversible monoamine oxidase B (MAO-B) inhibitors. N-Methyl-N-(2-pentyl)propargylamine (M-2-PP) and N-methyl-N-(2-hexyl) propargylamine (2-HxMP), for example, are approximately fivefold more potent than I-deprenyl at inhibiting mouse brain MAO-B activity following oral administration. These inhibitors are nonaromatic compounds and are chemically quite different from other known MAO-B inhibitors. Some of their neurochemical and neuroprotective properties have been evaluated and compared with those of I-deprenyl. We have confirmed that these new inhibitors selectively inhibit MAO-B activity both in vitro and in vivo. 2-Phenylethylamine levels were substantially increased following administration of M-2-PP, but the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid were not affected except at high, nonselective doses. Chronic oral administration of I-deprenyl and M-2-PP causes selective inhibition of MAO-B activity and increases dopamine levels in mouse caudate. M-2-PP, like I-deprenyl, has been shown to be potent in protecting against MPTP-induced damage in the mouse. N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenaline neurotoxin, is not an MAO substrate. Its noradrenaline-depleting effects were substantially mitigated by I-deprenyl as well as by M-2-PP and 2-HxMP in the mouse hippocampus. Administration of 2-phenylethylamine, however, failed to reverse the effect of DSP-4. The neuroprotective effect of M-2-PP and 2-HxMP is apparently unrelated to the uptake of DSP-4. |
| Databáze: | OpenAIRE |
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