Demonstration of non-opioid sigma binding with (d)/sup 3/H-SKF 10047 in guinea pig brain
A non-opioid binding site to (d)/sup 3/H-SKF 10047 (N-allyl-normetazocine), the prototypic ligand for the sigma or PCP-like receptor, was demonstrated. The (d) isomer of /sup 3/H-SKF 10047 was used to demonstrate a stereospecific low affinity binding site with a K/sub d/ of 173nM. It was naloxone insensitive with an IC/sup 50/ of greater than 10,000nM, which defined it as non-opioid. Traditional mu compounds like morphine and FK 33824 were also inactive, with IC/sup 50/'s of greater than 10,000nM. Kappa compounds such as ethylketocyclazocine and U-50,488H were active as were all of the benzmorphans tested, with butorphanol the least active. The known antipsychotic haloperidol was the most active compound tested, with an IC/sup 50/ of 11nM. Other antipsychotics which demonstrated activity were chlorpromazine and pimozide. The atypical antipsychotic clozapine was inactive.
- Research Organization:
- Upjohn Co., Kalamazoo, MI
- OSTI ID:
- 5220727
- Journal Information:
- Res. Commun. Chem. Pathol. Pharmacol.; (United States), Journal Name: Res. Commun. Chem. Pathol. Pharmacol.; (United States) Vol. 2; ISSN RCOCB
- Country of Publication:
- United States
- Language:
- English
Similar Records
Evidence for a non-opioid sigma binding site din the guinea-pig myenteric plexus
sigma opiates and certain antipsychotic drugs mutually inhibit (+)-(/sup 3/H)SKF 10,047 and (/sup 3/H)haloperidol binding in guinea pig brain membranes
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIDEPRESSANTS
AZINES
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CONFIGURATION INTERACTION
DRUGS
GUINEA PIGS
HETEROCYCLIC COMPOUNDS
IN VITRO
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PSYCHOTROPIC DRUGS
PYRAZINES
RECEPTORS
RODENTS
TRITIUM COMPOUNDS
VERTEBRATES