Portal de Periódicos da CAPES

Two novel σ receptor ligands, BD1047 and LR172, attenuate cocaine-induced toxicity and locomotor activity

1999; Elsevier BV; Volume: 370; Issue: 3 Linguagem: Inglês

10.1016/s0014-2999(99)00113-2

1879-0712

Kari A. McCracken, Wayne D. Bowen, Brian R. de Costa, Rae R. Matsumoto,

Receptor Mechanisms and Signaling

The ability of cocaine to interact with σ receptors indicates that these sites may mediate the negative properties associated with cocaine use, such as toxicity and addiction. Previous studies have shown that the novel σ receptor ligand, BD1008 (N-[2-(3,4-dicholophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine), effectively protects against cocaine-induced convulsions and locomotor activity in mice. Therefore, BD1047 ([2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(diamino)ethylamine) and LR172 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-homopiperidinyl)ethylamine), two analogs of BD1008, were tested to determine if they also have anti-cocaine properties. Receptor binding assays showed that BD1047 and LR172 both have high affinities for σ receptors, but low to negligible affinities for dopamine, opioid, phencyclidine, and 5-HT2 sites. In behavioral studies, pretreatment of mice with BD1047 or LR172 reduced the convulsions, lethality, and locomotor activity produced by cocaine. The data indicates a possible role for σ receptor ligands in the treatment of cocaine overdose and addiction.