caa a22 4500 46325483X CHVBK 20180405153351.0 cr unu---uuuuu 170326e20070201xx s 000 0 eng 10.1007/s10571-006-9085-1 doi (NATIONALLICENCE)springer-10.1007/s10571-006-9085-1 Metabolism of N -Methyl, N -propargylphenylethylamine: Studies with Human Liver Microsomes and cDNA Expressed Cytochrome P450 (CYP) Enzymes [Elektronische Daten] [Katherine Rittenbach, Andrew Holt, Lei Ling, Jackie Shan, Glen Baker] Summary: 1. We used an in vitro screening procedure and studies with individual human liver microsomes and cDNA-expressed CYP enzymes to investigate the metabolism of the putative neuroprotective drug N-methyl,N-propargyl-2-phenylethylamine (MPPE) to N-methylphenylethylamine (N-methylPEA) and N-propargylphenylethylamine (N-propargylPEA). 2. An electron-capture gas chromatographic procedure previously developed in our laboratories was used to measure the quantities of N-methylPEA and N-propargylPEA formed in the experiments with a single donor human liver microsome panel and cDNA expressed single CYP enzyme systems. The data were fitted to nonlinear regressions using Prism to determine kinetic constants. The results from a fluorogenic screen determined which cDNA-expressed single CYP enzymes were investigated. 3. CYP2B6, CYP2C19, and CYP2D6 all contributed to the formation of N-methylPEA, while only CYP2B6 catalyzed the formation of N-propargylPEA. The K M and V max values for N-propargylPEA formation were 290 ± 70μM and 139±16ng/mL/min. The values for formation of N-methylPEA were not determined from these experiments due to the complexity of fitting the data to a three-variable equation, but data on the time course of N-methylPEA formation are presented. 4. Catabolism of MPPE to N-methylPEA and N-propargylPEA is catalyzed by CYP enzymes. CYP2B6, 2C19 and 2D6 all contribute to the depropargylation of the parent compound, but only CYP2B6 also catalyzes demethylation. CYP2C19 was found to be the most active with respect to generation of N-methylPEA. Springer Science+Business Media, Inc., 2006 Human liver microsomes nationallicence N -methyl, N -propargylphenylethylamine (MPPE) nationallicence CYP enzymes nationallicence (−)-deprenyl nationallicence Metabolism nationallicence Rittenbach Katherine Neurochemical Research Unit, Department of Psychiatry, University of Alberta, 1E7.31 Mackenzie Centre, T6G 2R7, Edmonton, Alberta, Canada aut Holt Andrew Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada aut Ling Lei CV Technologies, Edmonton, Alberta, Canada aut Shan Jackie CV Technologies, Edmonton, Alberta, Canada aut Baker Glen Neurochemical Research Unit, Department of Psychiatry, University of Alberta, 1E7.31 Mackenzie Centre, T6G 2R7, Edmonton, Alberta, Canada aut Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/2(2007-02-01), 179-190 0272-4340 27:2<179 2007 27 10571 https://doi.org/10.1007/s10571-006-9085-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-006-9085-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rittenbach Katherine Neurochemical Research Unit, Department of Psychiatry, University of Alberta, 1E7.31 Mackenzie Centre, T6G 2R7, Edmonton, Alberta, Canada aut NATIONALLICENCE 700 1- Holt Andrew Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada aut NATIONALLICENCE 700 1- Ling Lei CV Technologies, Edmonton, Alberta, Canada aut NATIONALLICENCE 700 1- Shan Jackie CV Technologies, Edmonton, Alberta, Canada aut NATIONALLICENCE 700 1- Baker Glen Neurochemical Research Unit, Department of Psychiatry, University of Alberta, 1E7.31 Mackenzie Centre, T6G 2R7, Edmonton, Alberta, Canada aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/2(2007-02-01), 179-190 0272-4340 27:2<179 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer