title: Novel sigma receptor ligands attenuate the locomotor stimulatory effects of cocaine.
abstract: Cocaine interacts with sigma receptors, suggesting that these sites are important for many of its behavioral effects. Therefore, two novel sigma 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 sigma1 and sigma2 sites, but a 250-fold or lower affinity for nine other receptors, making them among the most selective sigma 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 sigma receptors are involved in the behavioral effects of cocaine.
authors.affiliation: University of Oklahoma Health Sciences Center, College of Pharmacy, Department of Pharmacology and Toxicology, Oklahoma City 73190, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: McCracken
authors.forename: W D
authors.initials: WD
authors.lastname: Bowen
authors.forename: R R
authors.initials: RR
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005021:Ethylamines / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D017478:Receptors, Phencyclidine / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism