In treating
Parkinson's disease with
dopaminergic agonists, such as
pramipexole,
ropinirole,
pergolide,
rotigotine,
apomorphine, or
bromocriptine, it has been observed that a significant number of patients develop
impulse-control disorders, such as compulsive shopping,
pathological gambling, or hypersexuality. Because the
dopamine agonists have high affinities for the
dopamine D2 and D3 receptors, the
drug dissociation constants of these drugs at the functional high-affinity states of these receptors, namely D2High and D3High, were compared. The data show that, compared to the other
dopamine agonist drugs,
pramipexole has a relatively high selectivity for the
dopamine D3 receptor, as compared to D2, suggesting that the D3 receptor may be a primary target for
pramipexole. There is a trend showing that the proportion of
impulse-control disorders is related to the selectivity for D3 receptors over D2 receptors, with
pramipexole having the highest association with, or frequency of,
impulse-control disorders. While the number of studies are limited, the proportion of patients with impulse-control disorder in Parkinson patients treated with an add-on agonist were 32% for
pramipexole, 25% for
ropinirole, 16% for
pergolide, 22% for
rotigotine, 10% for
apomorphine, and 6.8% for
bromocriptine. Clinically, temporary replacement of
pramipexole by
bromocriptine may provide relief or reversal of the impulsive behavior associated with selective D3 stimulation by either
pramipexole or
ropinirole, while maintaining D2 stimulation needed for the anti-Parkinson action.