Electroencephalographic, behavioral and receptor binding correlates of phencyclinoids in the rat.
The pharmacology and structure-activity relationship of phencyclidine (PCP)-like drugs (phencyclinoids) were studied using electroencephalographic (EEG), behavioral and receptor binding techniques. The effects of PCP, 1-phenylcyclohexylamine HCl, N-methyl-1-phenycyclohexylamine HCl, N-ethyl-1-phenylcyclohexylamine HCl, N-(s-butyl)-1-phenylcyclohexylamine HCL, 1-(1-phenylcyclo-hexyl)-pyrrolidine HCl, 1-[1-(2-thienyl)cyclohexyl] piperidine HCl, 1-[1-(2-thienyl)cyclohexyl]-pyrrolidine HCl, ketamine and (+/-)-SKF 10047 were evaluated on the direct EEG and EEG spectra after acute i.v. injections (0.1-17.8 mg/kg). Similarities and differences were noted in the EEG dose-response curves. At lower doses of PCP and its analogs, low-amplitude theta waves predominated; however, at higher doses, high-amplitude, lower-frequency waves predominated. Qualitatively, the N-piperidine derivatives were similar to PCP and differed primarily in potency. The benzomorphan (+/-)-SKF 10047 produced only theta activity at doses up to 12.8 mg/kg. These EEG effects occurred in conjunction with overt behaviors including locomotion, stereotypy and ataxia, concurrently assessed via observer-based rating scales. A strong correlation (r = 0.98) was obtained between the EEG and behavioral effects and the IC50 values from [3H]PCP displacement experiments using crude rat brain homogenates.
Mattia
A
A
Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore.
Marquis
K L
KL
Leccese
A P
AP
el-Fakahany
E E
EE
Moreton
J E
JE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D004569:Electroencephalography; D005260:Female; D007275:Injections, Intravenous; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D017478:Receptors, Phencyclidine; D014316:Tritium
D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D014316:Tritium; D010622:Phencyclidine