Pharmacological potency and biodisposition of phencyclidine via inhalation exposure in mice.
The purpose of the present study was to characterize the pharmacological effects and biodisposition of phencyclidine (PCP) following inhalation exposure to mice. Results from these studies indicate that PCP was easily volatilized when heated in a glass pipe. Volatilization was efficient with no significant formation of pyrolytic products. Exposure to the volatilized PCP resulted in a dose-dependent impairment in motor performance in both the rotorod and inverted-screen tests. PCP was equally effective in disrupting performance on the inverted-screen and rotorod with ED50 values corresponding to the volatilization of 10.7 and 13.2 mumol, respectively. The time courses were comparable to those produced following intravenous (i.v.) administration of PCP. In order to determine the dose of drug absorbed by inhalation, mice were exposed to [3H]-PCP. The ED50 values of PCP following i.v. administration were 4.1 and 6.2 mumol/kg in the inverted screen and rotorod, respectively. The biodisposition of PCP following inhalation exposure was similar to that after i.v. injections. At doses that produced approximately 50% of the maximum motor impairment by either administration route, higher ratios of the total drug equivalents were found following i.v. injection than that after inhalation, with the brain/plasma ratios of 1.3 +/- 0.2 versus 0.58 +/- 0.02, and brain/body ratios 0.59 +/- 0.06 versus 0.35 +/- 0.1 for i.v. and inhalation, respectively. However, the brain/plasma ratios of the concentrations of PCP were similar, 1.1 versus 0.9. The body concentration of PCP equivalents that produced 50% of the maximum effect after inhalation was 4.7 +/- 0.6 mumol/kg. These results indicate that inhalation of PCP produces a similar pharmacological profile to that of i.v. administration and suggest that the drug is equipotent by these two administrations routes. Moreover, these findings are consistent with the observation that smoking is becoming the most common route of administration among drug users.
Meng
Y
Y
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0613, USA. ymeng@gems.vcu.edu
Lichtman
A H
AH
Bridgen
D T
DT
Martin
B R
BR
D000280:Administration, Inhalation; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009048:Motor Skills / Q000187:drug effects*; D010622:Phencyclidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects*; D014018:Tissue Distribution
D010622:Phencyclidine