EFFECTS OF THE IMMUNOSTIMULANT, LEVAMISOLE, ON OPIATE WITHDRAWAL AND LEVELS OF ENDOGENOUS OPIATE ALKALOIDS AND MONOAMINE NEUROTRANSMITTERS IN RAT-BRAIN

This report presents evidence that the immunostimulant drug levamisole , (-)-(S)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b] thiazole monohydro chloride, produced a significant elevation of endogeneous morphine and codeine levels in brain regions and peripheral organs and attenuated the effects of naltrexone-induced withdrawal in morphine-addicted rats . Levamisole also significantly altered the metabolism of norepinephri ne, dopamine, and serotonin in specific brain regions. These results s uggest that levamisole's attenuation of opiate withdrawal may be relat ed to its ability to increase endogeneous opiate alkaloid levels and/o r to alter central monoaminergic function. Levamisole does not have si gnificant affinity for opiate receptors. These results raise the intri guing possibility that agents such as levamisole, which elevate the le vels of the endogenous opiate alkaloids, might be useful for treating narcotic withdrawal. The mechanism for the immunostimulatory propertie s of agents such as levamisole and muramyl dipeptide (MDP) have not be en established. We suggest that the ability of MDP and levamisole to i ncrease endogenous opiate alkaloids may be related to their immunostim ulatory properties. [Neuropsychopharmacology 19:417-427, 1998] (C) 199 8 American College of Neuropsychopharmacology. Published by Elsevier S cience Inc.