Novel sigma receptor ligands attenuate the locomotor stimulatory effects of cocaine

Eur J Pharmacol. 1999 Jan 15;365(1):35-8. doi: 10.1016/s0014-2999(98)00876-0.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Cocaine / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Ethylamines / metabolism
  • Ethylamines / pharmacology*
  • Guinea Pigs
  • Male
  • Mice
  • Motor Activity / drug effects*
  • Piperazines / metabolism
  • Piperazines / pharmacology*
  • Pyrrolidines / metabolism
  • Pyrrolidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / metabolism
  • Receptors, Phencyclidine / drug effects
  • Receptors, Phencyclidine / metabolism
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism
  • Receptors, sigma / drug effects*
  • Receptors, sigma / metabolism

Substances

  • 1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine
  • Dopamine Uptake Inhibitors
  • Ethylamines
  • Piperazines
  • Pyrrolidines
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Receptors, Adrenergic, beta
  • Receptors, Dopamine D2
  • Receptors, Opioid
  • Receptors, Phencyclidine
  • Receptors, Serotonin
  • Receptors, sigma
  • BD 1008
  • Cocaine