Reinterpretation of the effect of haloperidol and ethanol on insulin secretion

We were unable to confirm the report of haloperidol induced dose-dependent inhibition of insulin and glucagon release from the isolated canine pancreas. The possibility that the inhibition was caused by ethanol, previously used as the solvent for haloperidol, was tested. Infusion of ethanol at increasing concentrations (15.8 to 252 mmol/l) caused a progressive inhibition of insulin (-17 +/- 1 to -69 +/- 2%) and glucagon (-13 +/- 3 to -67 +/- 3%) secretion, using a perfusate containing 200 mg/dl glucose and 2.65 mmol/l calcium. Haloperidol (5 to 20 mumol/l) dissolved in ethanol (252 mmol/l) did not augment the inhibitory effects of ethanol. At a low calcium concentration (1.3 mmol/l) ethanol further inhibited insulin secretion (-83 +/- 2%) with no additional inhibition by 20 mumol/l haloperidol (-80 +/- 3%). At a high calcium concentration (8.8 mmol/l) the inhibitory effect of ethanol on insulin or glucagon secretions was diminished and variable. This strongly suggests that the inhibition of insulin and glucagon secretion previously attributed to haloperidol was caused by the ethanol solvent.