Bromocriptine-induced behavioral hypersensitivity: implications for the therapy of parkinsonism.

Bromocriptine (CB-154) is a direct-acting dopamine agonist of proven clinical efficacy in parkinsonism. The capacity of bromocriptine to induce receptor site hypersensitivity was investigated utilizing a behavioral model in guinea pigs. Following 4 weeks of bromocriptine treatment, animals demonstrated a subsequent long-lasting hypersensitivity to amphetamine and apomorphine. The data suggest that chronic use of bromocriptine can induce receptor site hypersensitivity. These results may be an indication that, because of a similar propensity to side effects during chronic therapy, direct-acting dopamine agonists will offer no long-term advantage over current antiparkinsonian drugs. The observed phenomena suggest that chronic dopaminergic agonism may not be an ideal therapy for parkinsonism.