TY - JOUR
T1 - Pharmacokinetic and pharmacodynamic properties of some phencyclidine analogs in rats
AU - Cho, Arthur K.
AU - Masayuki Hiramatsu, Hiramatsu
AU - Schmitz, Debra A.
AU - Toshitaka Nabeshima, Nabeshima
AU - Tsutomu Kameyama, Kameyama
N1 - Funding Information:
Male Sprague-Dawley derived rats (Charles River Breeding Laboratories, Wilmington, MA) weighing 230 to 360 g were 1This research was supported by USPHS research grant DA 02411. 2portions of this research have been presented at the Satellite Symposium of the 17th Congress of Collegium Internationale Neuro-Psychopharmaco-logicum: NMDA Related Agents: Biochemistry, Pharmacology and Behavior, Sept. 15-17, 1990, Nagoya, Japan.
PY - 1991/8
Y1 - 1991/8
N2 - The pharmacodynamics and pharmacokinetics of three phencyclidine analogs, differing from phencyclidine (PCP) only in the nature of the amine structure, were determined after intravenous doses of equimolar amounts to rats. The purpose of the study was to assess the role of pharmacokinetics in the in vivo potency of the compounds. The compounds examined were phenylcyclohexyl-pyrrolidine (PCPY), diethylamine (PCDE), ethylamine (PCE), and phencyclohexylamine (PCA). The behavior responses monitored included ataxia and others previously shown to be characteristic of PCP. In contrast to their relative affinities for the MK 801 binding site, the behavioral potencies of PCE, PCDE and PCPY were comparable to PCP. The major discrepancy occurred with PCDE, whose affinity for the NMDA receptor was 1 2th of PCP. The pharmacokinetic studies showed that the discrepancy between in vivo and in vitro activity of PCDE could be partially accounted for by its conversion to PCE, a relatively potent PCP-like agent.
AB - The pharmacodynamics and pharmacokinetics of three phencyclidine analogs, differing from phencyclidine (PCP) only in the nature of the amine structure, were determined after intravenous doses of equimolar amounts to rats. The purpose of the study was to assess the role of pharmacokinetics in the in vivo potency of the compounds. The compounds examined were phenylcyclohexyl-pyrrolidine (PCPY), diethylamine (PCDE), ethylamine (PCE), and phencyclohexylamine (PCA). The behavior responses monitored included ataxia and others previously shown to be characteristic of PCP. In contrast to their relative affinities for the MK 801 binding site, the behavioral potencies of PCE, PCDE and PCPY were comparable to PCP. The major discrepancy occurred with PCDE, whose affinity for the NMDA receptor was 1 2th of PCP. The pharmacokinetic studies showed that the discrepancy between in vivo and in vitro activity of PCDE could be partially accounted for by its conversion to PCE, a relatively potent PCP-like agent.
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U2 - 10.1016/0091-3057(91)90058-A
DO - 10.1016/0091-3057(91)90058-A
M3 - Article
C2 - 1837152
AN - SCOPUS:0026091167
SN - 0091-3057
VL - 39
SP - 947
EP - 953
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
IS - 4
ER -