REDUCTION OF HYPERGLYCEMIA AFTER ORAL GLUCOSE-LOAD BY THE NEW ALPHA(2)-ADRENERGIC RECEPTOR ANTAGONIST SL84.0418 IN HEALTHY-SUBJECTS

Objective: To assess the antihyperglycemic activity of a new periphera lly acting alpha2-adrenergic receptor antagonist, SL 84.0418 in health y volunteers Methods: This was a randomized, double-blind crossover st udy. The effects of 10, 50, and 100 mg SL 84.0418 on blood glucose, pl asma insulin, C-peptide, glucagon, epinephrine, and norepinephrine wer e investigated in comparison with placebo and 5 mg glipizide before an d after an oral glucose challenge (75 gin). Results: Peak blood glucos e and area under the blood-glucose curve were dose-dependently reduced by SL 84.0418; the extent of this reduction was similar with 100 mg S L 84.0418 and glipizide. Glipizide but not SL 84.0418 decreased nadir blood glucose. Plasma insulin and C-peptide were increased by glipizid e but not by SL 84.0418. Treatments did not modify plasma glucagon. Pl asma epinephrine increased during glipizide treatment and plasma norep inephrine increased during treatment with 50 and 100 mg SL 84.0418. Sy stolic and diastolic blood pressure were moderately enhanced by 50 and 100 mg SL 84.0418. Adverse effects reflecting alpha2-adrenergic recep tor blockade occurred more frequently with 100 mg SL 84.0418. The adve rse effect profile of 50 mg SL 84.0418 was not different from that obs erved with glipizide. Conclusion: The alpha2-adrenergic receptor antag onist SL 84.0418 dose dependently reduced the increase in blood glucos e after glucose load without modification of plasma insulin. It may re present an alternative to sulfonylureas in the treatment of non-insuli n-dependent diabetes mellitus. Further studies are needed to assess it s efficacy and tolerability in non-insulin-dependent patients.