Stereoselectivity and isoenzyme selectivity of monoamine oxidase inhibitors. Enantiomers of amphetamine, N-methylamphetamine and deprenyl |
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| Authors: | J B Robinson |
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| Institution: | 1. Physics Division, Lawrence Livermore National Laboratory, Livermore, CA 94550-9234, USA;2. Astronomisches Institut, Ruhr-Universität Bochum, D-44780 Bochum, Germany;3. MPI für Kernphysik, 69117 Heidelberg, Germany;1. Univ. Lille, Inserm, CHU Lille, U 1008—Controlled Drug Delivery Systems and Biomaterials, F-5900 Lille, France;2. Laboratório de Desenvolvimento Galênico, Nanobiotecnologia e Tecnologia Farmacêutica, Universidade Federal de Ouro Preto, Morro do Cruzeiro, 35400-000 Ouro Preto, Brazil;3. Univ. Lille, Faculté d’Ingénierie et Management de la Santé (ILIS), 42 rue Ambroise Paré, F-59120 Loos, France;1. Department of Materials Engineering, Faculty of Engineering, Ferdowsi University of Mashhad (FUM), Mashhad 9177948564, Iran;2. Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran;3. Department of Computer Engineering, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad 9177948564, Iran;1. Department of Forensic Toxicology, Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine, Guangfu Xi Road 1347, Shanghai 200063, China;2. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25, Lane 2200, Xietu Road, Shanghai 200032, China;3. Shanghai Medical College, Fudan University, Dongan Road, Shanghai 200032, China;1. Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan;2. Forensic Autopsy Section, Medico-legal Consultation and Postmortem Investigation Support Center (MLCPI-SC), c/o Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan;3. Division of Legal Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan |
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| Abstract: | The enantiomers of amphetamine, N-methylamphetamine and deprenyl were studied, using a solubilised rat liver mitochondrial monoamine oxidase (MAO) preparation, as competitive inhibitors of MAO-A and MAO-B (5-hydroxytryptamine and beta-phenylethylamine as substrate respectively). Only in the case of deprenyl enantiomers inhibiting MAO-B was a preference shown towards the R]-configuration enantiomer justifying the use of R]-(-)-deprenyl (as compared to the racemate) for the specific inhibition of MAO-B. Recalculation of the observed Ki values in terms of the base form of the inhibitor indicated that the activity of all enantiomers fell within a narrow, approximately 25-fold range when inhibiting MAO-B. The selectivity of inhibition of MAO-B by R]-(-)-deprenyl cannot therefore be attributed to any specific structural features of the MAO-B isoenzyme form but rather to a lack of affinity of this enantiomer towards MAO-A. |
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