Reproductive and developmental toxicity of the dopamine agonist pergolide mesylate in mice

Pergolide (Permax, LY127809, CAS 66104-23-2) a dopamine agonist for the treatment of Parkinson's disease, was evaluated for reproductive and developmental toxicity. Pergolide was administered in the diet at levels of 0, 5, 15, or 50 ppm to male and female ICR mice. In the F0 generation, the males were treated for 9 weeks prior to mating and throughout mating. The females were treated for 2 weeks prior to mating and throughout mating, gestation, and location (postnatal segment only). Females assigned to the teratology segment were killed on gestation day 18 for evaluation of fetal viability, weights, and morphology. Females assigned to the postnatal component were allowed to deliver and maintain their offspring throughout a 21-day lactation period. One male and one female were selected from each litter to continue as the F1 generation. Possible exposure of the F1 generation to pergolide ended at weaning. Growth of the F1 animals was monitored and reproductive performance evaluated. Treatment-related effects in the F0 generation were consistent with the pharmacologic effects of a dopamine agonist. These effects included pregnancy blockage at the 50-ppm dietary level and dose-related body weight depression in lactating dams and suckling progeny at the 15- and 50-ppm dietary levels. An increase in progeny mortality at the 50-ppm dietary level was attributed to lactation failure of the treated dams. The F1 mice of the 15- and 50-ppm groups remained smaller than the control mice until termination at approximately 20 weeks of age, although weight gains following weaning were not depressed and no impairment of mating performance or fertility was observed.(ABSTRACT TRUNCATED AT 250 WORDS)