Effects of the immunostimulant, levamisole, on opiate withdrawal and levels of endogenous opiate alkaloids and monoamine neurotransmitters in rat brain.
This report present evidence that the immunostimulant drug levamisole, (-)-(S)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b] thiazole monohydrochloride, 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 norepinephrine, dopamine, and serotonin in specific brain regions. These results suggest that levamisole's attenuation of opiate withdrawal may be related to its ability to increase endogeneous opiate alkaloid levels and/or to alter central monoaminergic function. Levamisole does not have significant affinity for opiate receptors. These results raise the intriguing possibility that agents such as levamisole, which elevate the levels of the endogenous opiate alkaloids, might be useful for treating narcotic withdrawal. The mechanism for the immunostimulatory properties of agents such as levamisole and muramyl dipeptide (MDP) have not been established. We suggest that the ability of MDP and levamisole to increase endogenous opiate alkaloids may be related to their immunostimulatory properties.
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007978:Levamisole / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000378:metabolism / Q000633:toxicity*; D009206:Myocardium / Q000378:metabolism; D009294:Narcotics / Q000378:metabolism / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000701:Analgesics, Opioid; D015306:Biogenic Monoamines; D009294:Narcotics; D007978:Levamisole; D012701:Serotonin; D009020:Morphine; D004298:Dopamine; D009638:Norepinephrine