JO 1784, a potent and selective ligand for rat and mouse brain sigma-sites.
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.
Roman
F J
FJ
Jouveinal Laboratories, Fresnes, France.
Pascaud
X
X
Martin
B
B
Vauché
D
D
Junien
J L
JL
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta
D002934:Cinnamates; D003521:Cyclopropanes; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C012134:SK&F 10047; C012058:tenocyclidine; D010620:Phenazocine; D010622:Phencyclidine; C065310:igmesine