JO 1784, a potent and selective ligand for rat and mouse brain σ‐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.