Rotigotine is a potent agonist at dopamine D-1 receptors as well as at dopamine D-2 and D-3 receptors

Background and PurposeRotigotine acts as a dopamine receptor agonist with high affinity for the dopamine D-2, D-3, D-4 and D-5 receptors but with a low affinity for the dopamine D-1 receptor. We have investigated this further in radioligand binding and functional studies and compared the profile of rotigotine with that of other drugs used in the treatment of Parkinson's disease (PD). Experimental ApproachThe binding of rotigotine to human dopamine D-1, D-2, D-3, D-4 and D-5 receptors was determined in radioligand binding studies using [H-3]rotigotine and compared with that of standard antagonist radioligands. Functional interactions of rotigotine with human dopamine receptors was also determined. Key Results[H-3]rotigotine can be used as an agonist radioligand to label all dopamine receptor subtypes and this can be important to derive agonist affinity estimates. Rotigotine maintains this high affinity in functional studies at all dopamine receptors especially D-1, D-2 and D-3 receptors and, to a lesser extent, D-4 and D-5 receptors. Rotigotine, like apomorphine but unlike ropinirole and pramipexole, was a potent agonist at all dopamine receptors. Conclusions and ImplicationsRotigotine is a high-potency agonist at human dopamine D-1, D-2 and D-3 receptors with a lower potency at D-4 and D-5 receptors. These studies differentiate rotigotine from conventional dopamine D-2 agonists, used in the treatment of PD, such as ropinirole and pramipexole which lack activity at the D-1 and D-5 receptors, but resembles that of apomorphine which has greater efficacy in PD than other dopamine agonists but has suboptimal pharmacokinetic properties.

Jaar van publicatie:2015