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Laboratory of Clinical Studies, National Institute on Alcohol Abuse & Alcoholism, DICBR, Bethesda, MD 20892.
Several serotonin (5-HT) receptor antagonists with varying specificities for the 5-HT receptor types, were studied with regard to their effects on blood glucose levels in mice. The non-selective antagonists, metergoline and methysergide, proved to be hyperglycemic at doses commonly used to antagonize 5-HT receptors. In contrast, ritanserin (a 5-HT2 and 5-HT1c antagonist) and MDL 72222 (a 5-HT3 antagonist) were effective only at doses which surpassed the dose range considered to be selective for their respective receptors. The results suggest that 5-HT systems play a role in maintaining glucose homeostasis and that 5-HT1 receptors may be particularly important in this function. Furthermore, the inherent hyperglycemic properties of non-selective serotonin antagonists described here, are pertinent to studies using these agents to investigate glucose metabolism.
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