Abstract

Betahistine, and two of its putative metabolites, 2-(2-aminoethyl) pyridine and 2-(2-hydroxyethyl) pyridine have been compared for effects (at constant blood-flow rate) on vascular resistance in the forelimb of the dog. Betahistine and its N-demethyl derivative, 2-(2-aminoethyl) pyridine, were of equal or similar potency in decreasing vascular resistance at a dose range of 0.22 to 2.2 µmol/min. In contrast, 2-(2-hydroxyethyl) pyridine at doses up to 22 µmol/min and 2-pyridylacetic acid, a urinary metabolite of betahistine in the dog, at doses up to 22 µmol/min produced no demonstrable change in vascular resistance. After p.o. administration of betahistine (15 mg/kg b.wt. for eight days) the urine of male mongrel dogs contained acidic metabolitea in amounts corresponding by spectrophotometricestimate to 45% of betahistine administered. The presence of 2-pyridylacetate in the acidic metabolic fraction was demonstrated by chemical preparation of methyl 2-pyridylacetate picrate, which was compared with an authentic sample of synthetic compound.