JO 1784, a potent and selective ligand for rat and mouse brain sigma-sites

J Pharm Pharmacol. 1990 Jun;42(6):439-40. doi: 10.1111/j.2042-7158.1990.tb06588.x.

Abstract

JO 1784 ((+)-cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene) is a potent ligand for (+)-[3H]SKF 10,047 (2'-hydroxy-5,9-dimethyl-2-allyl-6,7-benzomorphan) binding sites in rat brain membrane preparations with an IC50 of 39 +/- 8 nM, which is comparable to that of haloperidol. The stereoisomer of JO 1784 is ten fold less potent. When administered to mice i.p. or p.o. JO 1784 displaced (+)-[3H]SKF 10,047 (5 muCi i.v.) from its sites in the brain with ID50 values of 1.2 and 3.5 mg kg-1, respectively. The high selectivity of JO 1784 for the sigma-binding site was assessed by its lack of significant affinity for more than 20 other sites including those for phencyclidine.

MeSH terms

  • Animals
  • Brain Chemistry / drug effects*
  • Cinnamates / pharmacology*
  • Cyclopropanes / pharmacology*
  • In Vitro Techniques
  • Male
  • Mice
  • Phenazocine / analogs & derivatives
  • Phenazocine / metabolism
  • Phencyclidine / analogs & derivatives
  • Phencyclidine / metabolism
  • Phencyclidine / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid, delta

Substances

  • Cinnamates
  • Cyclopropanes
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • SK&F 10047
  • tenocyclidine
  • Phenazocine
  • Phencyclidine
  • igmesine