Lack of neuroprotective effect of sigma receptor ligands in the neurotoxicity of p-chloroamphetamine in rat brain

Eur J Pharmacol. 1995 Oct 6;293(3):277-80. doi: 10.1016/s0922-4106(05)80055-0.

Abstract

We studied the mechanism of antagonism of p-chloroamphetamine-induced neurotoxicity by dextromethorphan. The pretreatment with potent and selective sigma receptor ligands, 4-phenyl-4-(1-phenylbutyl)piperidine (4-PPBP) and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100), did not alter the reduction of 5-hydroxytryptamine and 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the cerebral cortex by repeated administration of p-chloroamphetamine. These results suggest that sigma receptors might not play a significant role in the antagonism of p-chloroamphetamine-induced neurotoxicity by dextromethorphan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anisoles / pharmacology
  • Antitussive Agents / pharmacology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Dextromethorphan / pharmacology
  • Haloperidol / analogs & derivatives
  • Haloperidol / pharmacology
  • Hydroxyindoleacetic Acid / metabolism
  • Ligands
  • Male
  • Propylamines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, sigma / physiology*
  • Serotonin / metabolism
  • Serotonin Agents / toxicity*
  • p-Chloroamphetamine / antagonists & inhibitors
  • p-Chloroamphetamine / toxicity*

Substances

  • Anisoles
  • Antitussive Agents
  • Ligands
  • Propylamines
  • Receptors, sigma
  • Serotonin Agents
  • 4-phenyl-1-(4-phenylbutyl)piperidine
  • N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride
  • Serotonin
  • Hydroxyindoleacetic Acid
  • p-Chloroamphetamine
  • Dextromethorphan
  • Haloperidol