JO-1784, A POTENT AND SELECTIVE LIGAND FOR RAT AND MOUSE-BRAIN SIGMA-SITES

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 μCi 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 σ‐binding site was assessed by its lack of significant affinity for more than 20 other sites including those for phencyclidine. 1990 Royal Pharmaceutical Society of Great Britain