Pergolide mesylate is a potent
dopamine agonist that is being evaluated clinically in
Parkinson disease,
hyperprolactinemia, and other diseases.
Pergolide activates both presynaptic and postsynaptic
dopamine receptors, with some apparent selectivity for the presynaptic
dopamine autoreceptors. In rats, low doses of
pergolide (0.01 mg/kg or less, intraperitoneally) decreased
dopamine turnover in brain, decreased serum
prolactin concentration, and reduced blood pressure in spontaneously hypertensive rats. At somewhat higher doses (0.05 mg/kg or more, intraperitoneally),
pergolide caused contralateral turning in nigrostriatal-lesioned rats, elevation of serum
corticosterone, and hypermotility with stereotyped behavior. All of these actions are thought to be due to stimulation of
dopamine receptors at various sites, but the data suggest that
pergolide may have preferential affinity for presynaptic
dopamine receptors. If low doses of
pergolide can reduce dopaminergic transmission by activating
presynaptic receptors that control
dopamine release, then this action might be therapeutically useful in treating
schizophrenia without causing
tardive dyskinesia or in the treatment of
tardive dyskinesia. The long duration of action of
pergolide seen in animal and human studies could be an important advantage over some other
dopamine agonists such as
apomorphine.