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 (/sup 3/H)PCP displacement experiments using crude rat brain homogenates.
- Research Organization:
- Univ. of Maryland School of Pharmacy, Baltimore (USA)
- OSTI ID:
- 6864685
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 246:2; ISSN JPETA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AZINES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
DIAGNOSTIC TECHNIQUES
DOSE-RESPONSE RELATIONSHIPS
ELECTROENCEPHALOGRAPHY
HETEROCYCLIC COMPOUNDS
INJECTION
INTAKE
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PIPERAZINES
PROTEINS
PYRAZINES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES