Novel σ receptor ligands attenuate the locomotor stimulatory effects of cocaine

Cocaine interacts with a receptors, suggesting that these sites are important for many of its behavioral effects. Therefore, two novel a receptor Ligands, BD1008 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) and BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), were evaluated for their ability to attenuate cocaine-induced locomotor activity. Receptor binding studies showed that BD1008 and BD1063 have nanomolar affinities for sigma(1) and sigma(2) sites, but a 250-fold or lower affinity for nine other receptors, making them among the most selective a receptor ligands identified. In behavioral studies, pretreatment of mice with BD1008 or BD1063 produced a two-fold increase in the ED50 for the locomotor stimulatory effects of cocaine. These results suggest that a receptors are involved in the behavioral effects of cocaine. (C) 1999 Elsevier Science B.V. All rights reserved.