Tablets containing 25 mg. diphenidol, as the hydrochloride, in bottles of 100.
‘Vontrol’ (diphenidol, SK&F) exerts its antiemetic effect primarily by inhibiting the chemoreceptor trigger zone, as evidenced by its activity in blocking emesis induced by apomorphine in dogs. In this regard ‘Vontrol’, as the hydrochloride salt, has a potency equal to the potent phenothiazine antiemetic, chlorpromazine hydrochloride. In animals ‘Vontrol’ has only weak parasympatholytic activity and no significant sedative, tranquilizing or antihistaminic action or effects on blood pressure, heart rate, respiration or the electrocardiogram.
Subacute and chronic toxicity studies in rats and dogs, in which large doses of ‘Vontrol’, as the hydrochloride salt, were administered orally and intramuscularly for periods up to one year, revealed no significant effects on hematology, liver function, kidney function or blood glucose determinations. Histological examination of the animals’ tissues did not reveal any significant lesions attributable to administration of ‘Vontrol’.
Teratogenesis and reproduction studies were carried out in rats and rabbits. In rats, ‘Vontrol’ (diphenidol, SK&F), as the hydrochloride salt, was fed daily to male and female animals in doses of 20 mg./kg. and 40 mg./kg. (approximately three and six times the maximum recommended daily dose in adult humans) for 60 days before mating, and during mating, gestation and lactation for each of two litters. There were no significant differences between drug-treated and untreated control groups with regard to conception rate, litter size, live birth or viability in either of the two litters. There was no congenital anomaly among the offspring. In rabbits, ‘Vontrol’, as the hydrochloride salt, was fed in the diets in doses of 5 mg./kg. or 75 mg./kg. (approximately equal to, and 12 times as much as, the maximum recommended daily dose in adult humans) from the first day of gestation through the 26th or 27th day of gestation, when the young were delivered by Cesarean section. There were no significant differences between drug-treated and control groups with regard to number and weight of fetuses, numbers of resorption sites or viable fetuses. There was also no statistically significant difference between drug-treated and control groups with regard to the total percentage of underdeveloped fetuses. However, when data were calculated on the basis of a ratio between underdeveloped fetuses and number of pregnant does, an adverse dose-related effect was observed in the high-dose test group.