Electroencephalographic, behavioral and receptor binding correlates of phencyclinoids in the rat.
A. Mattia, Karen L. Marquis, A. Leccese, E. E. El-Fakahany, J. Moreton
Journal of Pharmacology and Experimental Therapeutics August 1, 1988 DOI: 10.1016/s0022-3565(25)22166-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical pharmacology study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | PCP 1-phenylcyclohexylamine HCl N-ethyl-1-phenylcyclohexylamine HCl N-(s-butyl)-1-phenylcyclohexylamine HCl 1-[1-(2-thienyl)cyclohexyl]-pyrrolidine HCl ketamine (+/-)-SKF 10047 |
| Dose | 0.1-17.8 mg/kg i.v. |
| Measures | EEG, EEG spectra, observer-based behavioral rating scales, [3H]PCP displacement IC50 |
| Key points | PCP and several analogs produced dose-dependent EEG changes, shifting from low-amplitude theta waves at lower doses to high-amplitude, lower-frequency waves at higher doses, alongside locomotion, stereotypy, and ataxia. The N-piperidine derivatives were qualitatively similar to PCP but differed in potency, and (+/-)-SKF 10047 produced only theta activity. EEG and behavioral effects correlated strongly (r = 0.98) with [3H]PCP displacement IC50 values, suggesting these effects are mediated by a common binding site. |
Abstract
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.