Dextro-naloxone counteracts amphetamine-induced hyperactivity

Pharmacol Biochem Behav. 1998 Feb;59(2):271-4. doi: 10.1016/s0091-3057(97)00528-5.


The locomotor stimulating effect of d-amphetamine in mice was counteracted by the administration of l-naloxone [(-)-naloxone], a known opiate receptor antagonist. Mice injected with amphetamine reached a peak locomotor activity within 30 min. When treated simultaneously with amphetamine and l-naloxone, these subjects showed low motility. Furthermore, when mice were treated not with l-naloxone but with its mirror image, d-naloxone [(+)-naloxone], a compound that by itself does not antagonize opiates and does not affect spontaneous motility, they showed no amphetamine-induced hyperactivity. The finding that an enantiomer of naloxone, with no opiate antagonist activity, is able to block the excitatory action of amphetamine, suggests the existence of a hitherto unknown mechanism of counteracting some of the effects of stimulants and euphoriants like amphetamine and cocaine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / antagonists & inhibitors*
  • Amphetamine / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Dopamine Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Morphine / pharmacology
  • Motor Activity / drug effects*
  • Naloxone / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Narcotics / pharmacology
  • Stereoisomerism


  • Dopamine Agents
  • Narcotic Antagonists
  • Narcotics
  • Naloxone
  • Morphine
  • Amphetamine