Structure-activity relationships of phencyclidine derivatives in rat cerebellum |
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| Authors: | K Pang S W Johnson S Maayani R Freedman |
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| Affiliation: | 1. Departments of Psychiatry and Pharmacology, University of Colorado School of Medicine, Denver, CO 80262, USA;2. Department of Pharmacology, Mt. Sinai School of Medicine of the City University of New York New York, NY 10029, USA;3. Denver Veterans Administration Medical Center, Denver CO 80262, USA;1. Process Technology Development Division, Defence Research & Development Establishment, Jhansi road, Gwalior 474 002, India;2. School of Studies in Chemistry, Jiwaji University, Gwalior, India;1. Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China;2. Department of Military Toxicology and Biochemical Pharmacology, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China;1. Institute for Pharmacy and Food Chemistry, Julius-Maximilians-University of Würzburg, Am Hubland, 97074 Würzburg, Germany;2. Medical Mission Institute, Hermann-Schell-Strasse 7, 97074 Würzburg, Germany;3. Institute for Pharmacy and Biochemistry, Johannes-Gutenberg-University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany;4. Institute for Molecular Infection Biology, Julius-Maximilians-University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany;5. Biochemistry Center (BZH), Heidelberg University, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany;1. Department of Medical Sciences, Pharmacology Section, University of Ferrara, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy;2. Department of Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy;1. National Poison Control Centre, Military Medical Academy, University of Defence, Belgrade, Serbia;2. Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, Banja Luka, Republic of Srspka, Bosnia and Herzegovina;3. Experta Consulting, Belgrade, Serbia;4. Department of Anatomy and Forensic Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia;1. College of Pharmaceutical sciences, Zhejiang University of Technology, Hangzhou, PR China;2. Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, PR China |
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| Abstract: | The depressant effects of phencyclidine [1-(1-phenylcyclohexyl) piperidine, PCP] and three of its analogs (m-amino-PCP, m-nitro-PCP, and PCP-methyliodide) on the spontaneous action potential discharge of cerebellar Purkinje neurons in urethane-anesthetized rats were examined in this study. Both intraperitoneal injection and micro-pressure ejection were employed as routes of drug administration. The relative potency after parenteral administration corresponded closely with previous findings in behavioral test paradigms. PCP and m-amino-PCP were equipotent, m-nitro PCP was less potent than either PCP or m-amino-PCP, and PCP-methyliodide showed almost no activity. After local administration onto neurons, m-amino-PCP was significantly more potent than PCP, while PCP, m-nitro-PCP, and PCP-methyliodide were equipotent. Tritiated PCP, m-nitro PCP, and m-amino PCP have similar distribution and metabolism in cerebellum. PCP-methyliodide, a quaternary ion, does not cross the blood brain barrier. M-nitro PCP is appreciably less ionized at pH 7.4 than PCP or m-amino-PCP and, therefore, may be more easily sequestered into lipids. Differences between PCP and its analogs found in experiments which employ parenteral administration may reflect differences in drug distribution. These differences are minimized when these drugs are administered directly onto neurons via pressure microejection. |
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