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SM Owens, M Zorbas, DL Lattin, M Gunnell and M Polk
Department of Pharmacology and Interdisciplinary Toxicology, University of Arkansas for Medical Sciences, Little Rock.
Rabbit antibodies were generated against five unique epitopes of phencyclidine (PCP)-like molecules to determine the molecular requirements for arylcyclohexylamine binding to the PCP receptor. Three of the haptens contained the three ring structures of PCP. A fourth hapten was synthesized from a derivative of the highly potent PCP analog, 1-[1-(2-thienyl)cyclohexyl]piperidine. The fifth hapten, 5-[N- (1'-phenylcyclohexyl)amino]pentanoic acid, was used as a haptenic model for N-ethyl-1-phenylcyclohexylamine, one of the most potent arylcyclohexylamines. These haptens were bound covalently to bovine serum albumin and were then used as antigens to immunize rabbits. The affinities and cross-reactivity patterns of the resulting five antibodies were studied in a [3H]PCP radioimmunoassay using standard curves of various arylcyclohexylamines. The dissociation constants ranged from 1.9 to 51.6 nM. From the average IC50 values of the radioimmunoassay dose-response curves, the relative potency of each ligand to PCP was determined. Least-squares linear regression was used to correlate these data with relative potency data from two [3H]PCP receptor binding assays and a PCP drug discrimination assay in the rat. Only relative potency data from the anti-5[N-(1'- phenylcyclohexyl)amino]pentanoic acid antibody showed a significant correlation with data from the three pharmacological studies (r2 = 0.80, 0.57 and 0.78, respectively; p less than .05 in all cases). These data indicated the 5-[N-(1'-phenylcyclohexyl)amino]pentanoic acid hapten contained the pharmacologically active features needed for arylcyclohexylamine binding to the PCP receptor.
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  E. C. Peterson, E. M. Laurenzana, W. T. Atchley, H. P. Hendrickson, and S. M. Owens Development and Preclinical Testing of a High-Affinity Single-Chain Antibody against (+)-Methamphetamine J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 124 - 133. [Abstract] [Full Text] [PDF]
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E. C. Peterson, M. Gunnell, Y. Che, R. L. Goforth, F. I. Carroll, R. Henry, H. Liu, and S. M. Owens Using Hapten Design to Discover Therapeutic Monoclonal Antibodies for Treating Methamphetamine Abuse J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 30 - 39. [Abstract] [Full Text] [PDF]
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 M. I. Jushchyshyn, U. M. Kent, and P. F. Hollenberg The Mechanism-Based Inactivation of Human Cytochrome P450 2B6 by Phencyclidine Drug Metab. Dispos., January 1, 2003; 31(1): 46 - 52. [Abstract] [Full Text] [PDF]
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J. Chun, U. M. Kent, R. M. Moss, L. M. Sayre, and P. F. Hollenberg Mechanism-Based Inactivation of Cytochromes P450 2B1 and P450 2B6 by 2-Phenyl-2-(1-piperidinyl)propane Drug Metab. Dispos., August 1, 2000; 28(8): 905 - 911. [Abstract] [Full Text]
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 K. Lim, S. M. Owens, L. Arnold, J. C. Sacchettini, and D. S. Linthicum Crystal Structure of Monoclonal 6B5 Fab Complexed with Phencyclidine J. Biol. Chem., October 30, 1998; 273(44): 28576 - 28582. [Abstract] [Full Text] [PDF]
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J. S. Hardin, W. D. Wessinger, J. W. Proksch, and S. M. Owens Pharmacodynamics of a Monoclonal Antiphencyclidine Fab with Broad Selectivity for Phencyclidine-Like Drugs1 J. Pharmacol. Exp. Ther., June 1, 1998; 285(3): 1113 - 1122. [Abstract] [Full Text]
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