PT - JOURNAL ARTICLE AU - S M Owens AU - M Zorbas AU - D L Lattin AU - M Gunnell AU - M Polk TI - Antibodies against arylcyclohexylamines and their similarities in binding specificity with the phencyclidine receptor. DP - 1988 Aug 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 472--478 VI - 246 IP - 2 4099 - http://jpet.aspetjournals.org/content/246/2/472.short 4100 - http://jpet.aspetjournals.org/content/246/2/472.full SO - J Pharmacol Exp Ther1988 Aug 01; 246 AB - 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.