Pergolide is a synthetic ergot derivative and is a potent, long-acting dopamine receptor agonist. Both in vitro and in vivo pharmacological studies have demonstrated the activity of pergolide as a selective dopamine agonist with little or no effect on norepinephrine, epinephrine or serotonin pathways at therapeutic doses. As with other dopamine agonists, pergolide inhibits the release of prolactin. In horses with Pituitary Pars Intermedia Dysfunction (PPID) pergolide exerts its therapeutic effect by stimulating dopamine receptors. Further, in horses with PPID, pergolide has been shown to decrease the plasma levels of ACTH, MSH and other pro-opiomelanocortin peptides.

Pharmacokinetic information in the horse is available for oral doses of 2, 4 and 10 μg pergolide/kg body weight. It has been demonstrated that pergolide is rapidly absorbed with a short time to peak concentration.

Peak concentrations (Cmax) following the dose of 10 μg/kg were low and variable with a mean of ~ 4 ng/ml and a mean terminal half-life (T ½) of ~ 6 hours. The median time of peak concentration (Tmax) was ~ 0.4 hours and the area under the curve (AUC) was ~ 14 ng x hours/ml.

In a more sensitive analytical assay, plasma concentrations following the dose of 2 μg pergolide/kg were very low and variable with peak concentrations ranging from 0.138-0.551 ng/ml. The peak concentrations occurred at 1.25+/-0.5 hours (Tmax). Plasma concentrations in most horses were quantifiable for only 6 hours post dose. However, one horse had quantifiable concentrations for 24 hours. Terminal half-lives were not calculated as there was incomplete elucidation of the plasma concentration-time curve for most horses.

Peak concentrations (Cmax) following the dose of 4 µg/kg were low and variable with a range from 0.4–4.2 ng/mL with a mean of 1.8 ng/mL, and a mean terminal half-life (T ½) of ~ 6 hours. The median time of peak concentration (Tmax) was ~ 0.6 hours and the AUCt ~ 3.4 ng x h/ml.

Pergolide mesilate is approximately 90% associated with plasma proteins in humans and laboratory animals. The route of elimination is via the kidneys.