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J Pharmacol Sci. 2003 Sep;93(1):74-9.

The tricyclic antidepressant clomipramine increases plasma glucose levels of mice.

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Department of Pharmacology, Kobe Pharmaceutical University, Higashinada-ku. Japan.


Effects of the tricyclic antidepressant clomipramine on plasma glucose levels in mice were studied. Clomipramine at doses ranging 5 - 20 mg/kg elicited significant hyperglycemia in mice. Hyperglycemia elicited by clomipramine was not reduced by pretreatment with the 5-hydroxytryptamine (5-HT) depleter p-chlorophenylalanine. The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it. The 5-HT(2B/2C)-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the 5-HT(2A)-receptor antagonist ketanserin was without effect. Clomipramine-induced hyperglycemia was reduced by prior adrenalectomy. These results suggest that clomipramine induces hyperglycemia in mice by blocking the 5-HT(2B )and/or 5-HT(2C) receptors, which results in facilitation of adrenaline release.

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