MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease
| Autor: | Ph. Bey, Michael G. Palfreyman, Ian A. McDonald, Mark W. Dudley, John R. Fozard, Monique Zreika |
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| Rok vydání: | 1989 |
| Předmět: |
Male
Monoamine Oxidase Inhibitors Administration Oral Pharmacology Butylamines Mice chemistry.chemical_compound Oral administration Animals Parkinson Disease Secondary Monoamine Oxidase IC50 Biological Psychiatry ED50 chemistry.chemical_classification Dose-Response Relationship Drug General Neuroscience MPTP MPTP Poisoning Rats Inbred Strains Tyramine In vitro Rats Allyl Compounds Psychiatry and Mental health Enzyme Neurology chemistry Neurology (clinical) Monoamine oxidase B |
| Zdroj: | Journal of Neural Transmission - Parkinson's Disease and Dementia Section. 1:243-254 |
| ISSN: | 1435-1463 0936-3076 |
| DOI: | 10.1007/bf02263478 |
| Popis: | MDL 72,974, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine, was designed to be a selective inhibitor of monoamine oxidase type B (MAO-B). In vitro, the compound inhibits rat brain mitochondrial MAO in a concentration and time-dependent fashion and shows marked selectivity for the B form (IC50 = 680 and 3.6 nM for MAO-A and MAO-B, respectively). After oral administration to rats, the compound shows preferential inhibition of brain MAO-B with ED50 values of 8 and 0.18 mg/kg p.o. for the A and B forms, respectively. Selectivity is retained on repeat dosing. MDL 72,974 did not significantly potentiate the cardiovascular effects of intraduodenually-administered tyramine in anaesthetized rats and had only minor indirect sympathomimatic effects in the pithed rat. At MAO-B selective doses the neurotoxic effect of MPTP in mice was blocked. |
| Databáze: | OpenAIRE |
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