Failure of ergotamine to act as an amplifier of sulfonylurea-stimulated insulin secretion

Summary

Normal dogs were injected i.v. with 0.25 mg/kg sodium salt of HB 419 (gliben-clamide) and plasma insulin concentrations were measured over a period of 2 hrs. When the animals were given a single i.v. injection of 0.2 mg/kg dihydroergotamine tartrate (DHE) 30 min prior to the administration of HB 419, the insulinogenic effect of the sulfonylurea was considerably amplified (192 µU/mlvs 34 µU/mI at 45 min). No augmentation of the insulinogenic effect of HB 419 was observed when the same experiments were conducted with 0.05, 0.025 or 0.01 mg/kg ergotamine tartrate. At the dose level of 0.1 mg/kg the insulinogenic effect of HB 419 was suppressed. Since the structural difference between these two ergor alkaloids consists of the presence or absence of the double bond at C₉ and C₁₀ of the lysergic acid moiety, it appears that saturation of this double bond is an essential structural requirement for DHE to function as an amplifier of sulfonylurea-stimulated insulin release.