Dextro-naloxone counteracts amphetamine-induced hyperactivity

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.