Chapter title |
Haloallylamine inhibitors of MAO and SSAO and their therapeutic potential.
|
---|---|
Chapter number | 54 |
Book title |
Amine Oxidases: Function and Dysfunction
|
Published in |
Journal of neural transmission Supplementum, January 1994
|
DOI | 10.1007/978-3-7091-9324-2_54 |
Pubmed ID | |
Book ISBNs |
978-3-21-182521-1, 978-3-70-919324-2
|
Authors |
M G Palfreyman, I A McDonald, P Bey, C Danzin, M Zreika, G Cremer, M. G. Palfreyman, I. A. McDonald, P. Bey, C. Danzin, M. Zreika, G. Cremer, Palfreyman, M. G., McDonald, I. A., Bey, P., Danzin, C., Zreika, M., Cremer, G. |
Abstract |
Based on mechanistic understandings, molecular modeling and extensive quantitative structure-activity relationships, appropriately substituted haloallylamine derivatives were designed as potential mechanism-based inhibitors of MAO and/or SSAO. Potent inhibition of MAO-B and SSAO occurred with fluoroallylamines whereas chloroallylamines, such as MDL 72274A ((E)-2-phenyl-3-chloroallylamine hydrochloride), were selective and potent inhibitors of SSAO. MDL 72974A (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride is a potent (IC50 = 10(-9) M) inhibitor of both MAO-B and SSAO, with 190-fold lower affinity for MAO-A. In clinical studies, oral doses as low as 100 micrograms produced substantial inhibition of platelet MAO-B. Essentially complete inhibition occurred at 1 mg with the effect lasting 6-10 days. One or 4 mg MDL 72974A given daily for 28 days to 40 Parkinson's patients treated with L-dopa produced statistically significant reductions in the Unified Parkinson's Disease Rating Scale. MAO-B inhibitors, such as MDL 72974A and L-deprenyl, offer the potential of being neuroprotective in Parkinson's Disease and other neurogenerative disorders. Concommitant inhibition of SSAO may provide additional, but as yet unproven, advantages over pure inhibitors of MAO-B. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 14 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 4 | 29% |
Student > Ph. D. Student | 2 | 14% |
Professor | 1 | 7% |
Other | 1 | 7% |
Lecturer | 1 | 7% |
Other | 1 | 7% |
Unknown | 4 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 14% |
Biochemistry, Genetics and Molecular Biology | 2 | 14% |
Agricultural and Biological Sciences | 2 | 14% |
Nursing and Health Professions | 1 | 7% |
Psychology | 1 | 7% |
Other | 2 | 14% |
Unknown | 4 | 29% |