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Hyperglycemic effect of lidamidine in the rat
1Department of Gastrointestinal Pharmacology, William H. Rorer, Inc., Fort Washington, Pennsylvania.
Archives Internationales De Pharmacodynamie Et De Therapie
|August 1, 1987
Summary
Lidamidine, an antidiarrheal drug, causes hyperglycemia in rats by activating alpha 2-adrenoceptors, which inhibit insulin release from pancreatic beta-cells. This effect is reversible with insulin administration.
Area of Science:
- Pharmacology
- Endocrinology
- Physiology
Background:
- Lidamidine is a novel antidiarrheal agent.
- Understanding the physiological mechanisms of drug-induced hyperglycemia is crucial for patient safety and therapeutic development.
Purpose of the Study:
- To investigate the mechanism underlying the hyperglycemic effect of lidamidine.
- To determine the role of adrenoceptors and insulin in lidamidine-induced hyperglycemia.
Main Methods:
- Oral administration of lidamidine to fed rats.
- Assessment of plasma glucose levels over time.
- Studies in alloxanized rats (to assess insulin dependency).
- Evaluation of the effects of insulin administration and alpha- and beta-adrenoceptor antagonists (yohimbine, RX781094A, prazosin, propranolol) and hexamethonium.
Main Results:
- Lidamidine caused a dose-dependent, sustained increase in plasma glucose levels in fed rats.
- The hyperglycemic effect was absent in alloxanized rats and prevented by insulin administration.
- Pretreatment with alpha 2-adrenoceptor antagonists (yohimbine, RX781094A) blocked the hyperglycemia; other antagonists had no effect.
Conclusions:
- Lidamidine induces hyperglycemia through the activation of peripheral alpha 2-adrenoceptors.
- This activation inhibits insulin release from pancreatic beta-cells, leading to elevated plasma glucose.
- Lidamidine's hyperglycemic effect is insulin-dependent and mediated by specific adrenoceptor pathways.