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Related Experiment Videos

Phencyclidine/SKF-10,047 binding sites: evaluation of function.

D J McCann1, R A Rabin, S Rens-Domiano

  • 1Department of Pharmacology and Therapeutics, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.

Pharmacology, Biochemistry, and Behavior
|January 1, 1989
PubMed
Summary
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Phencyclidine (PCP) and (+)SKF-10,047 effects are linked to TCP binding sites, suggesting these sites mediate PCP

Area of Science:

  • Neuropharmacology
  • Behavioral Neuroscience
  • Receptor Binding Assays

Background:

  • Phencyclidine (PCP) is a dissociative anesthetic with complex psychopharmacological effects.
  • Understanding the specific neurochemical targets of PCP and related compounds is crucial for elucidating their mechanisms of action.
  • Previous research has identified various binding sites, but their precise roles in mediating behavioral effects remain under investigation.

Purpose of the Study:

  • To investigate the involvement of specific binding sites in the discriminative stimulus properties and behavioral effects of PCP and (+)SKF-10,047.
  • To compare the affinities of PCP and its analogs at different binding sites with their observed potencies in behavioral tasks.
  • To characterize the pharmacological properties and cellular localization of haloperidol-sensitive (+)[3H]SKF-10,047 binding sites (H-S-SKF sites).

Related Experiment Videos

Main Methods:

  • Correlation analyses were performed comparing rank-order affinities and rank-order potencies of (+)SKF-10,047, PCP, and several PCP analogs.
  • Binding assays were utilized to assess drug affinities at [3H]-1-[1-(2-thienyl)cyclohexyl]piperidine binding sites (TCP sites) and H-S-SKF sites.
  • Behavioral studies, including a 4-arm radial maze task, were conducted to determine drug potencies in producing specific behavioral outcomes like 180-degree perseveration.

Main Results:

  • A significant relationship was found between drug affinities at TCP sites and their potencies in mediating PCP's discriminative stimulus properties and 180-degree perseveration.
  • No significant correlation was observed between drug affinities at H-S-SKF sites and their potencies.
  • H-S-SKF sites demonstrated a lack of pharmacological selectivity and were localized in the microsomal fraction of cells.

Conclusions:

  • TCP sites are likely involved in mediating the behavioral effects of both PCP and (+)SKF-10,047, suggesting a common receptor target.
  • H-S-SKF sites may not be directly involved in mediating the observed behavioral effects of these compounds.
  • The pharmacological profile of H-S-SKF sites suggests they might represent a type of membrane-bound enzyme rather than a classical neurotransmitter receptor.