Parkinson's disease treatment may cause impulse–control disorder via dopamine D3 receptors

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Abstract

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. Synapse, 69:183–189, 2015. © 2015 Wiley Periodicals, Inc.

The dopamine D2 receptor can exist in a state of high-affinity for dopamine (D), as D2High, or in a state of low affinity for dopamine, as D2Low. The same holds for the D3 receptor. Agonists, such as pramipexole (P) that are highly selective for D3High, as compared to D2High, are associated with a high proportion of impulse–control disorders in agonist-treated Parkinson patients.

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