Short-term influence of a post-synaptic alpha-adrenoceptor blocking drug (prazosin) on carbohydrate metabolism

Since sympathetic nervous activity is intimately involved in the regulation of hormonal and metabolic responses, it may be assumed tht antihypertensive drugs acting on adrenergic receptors will interfere with metabolic control mechanisms. We have therefore evaluated the effect of the selective alpha 1-adrenoceptor blocker prazosin on intravenous glucose tolerance and insulin response in a group of 6 healthy subjects. Ninety minutes after a single oral dose of 2 mg prazosin we observed a significant (p less than 0.05) fall in K-value (mean decrease from 1.7 to 1.0), which was accompanied by a blunting of the early insulin response. The acute effects of prazosin closely resemble those observed after 6-8 weeks of treatment with therapeutic doses of prazosin in hypertensive women. It is postulated that the effect of prazosin is mediated by an increase in circulating catecholamines acting on the pancreatic beta-cell alpha 2-adrenoceptors, which are responsible for the well-known inhibitory action of alpha-adrenergic agents upon the release of insulin.