Rotigotine is a potent agonist at dopamineD1receptors as well as at dopamineD2andD3receptors

• DOI: 10.1111/bph.12988
• Publication Date: 2014-10-23T04:30:16Z
• Authors: Martyn Wood; Vanessa Dubois; Dieter Scheller; Michel Gillard
• Keywords: Radioligand Assay; 03 medical and health sciences; 0302 clinical medicine; Tetrahydronaphthalenes; Dopamine Agonists; Humans; Thiophenes; 3. Good health; Cell Line; Receptors, Dopamine

Background and PurposeRotigotine acts as a dopamine receptor agonist with high affinity for the dopamineD2,D3,D4andD5receptors but with a low affinity for the dopamineD1receptor. 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 ofParkinson's disease (PD).Experimental ApproachThe binding of rotigotine to human dopamineD1,D2,D3, D4andD5receptors was determined in radioligand binding studies using [3H]rotigotine and compared with that of standard antagonist radioligands. Functional interactions of rotigotine with human dopamine receptors was also determined.Key Results[3H]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 especiallyD1,D2andD3receptors and, to a lesser extent,D4andD5receptors. 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 dopamineD1,D2andD3receptors with a lower potency atD4andD5receptors. These studies differentiate rotigotine from conventional dopamineD2agonists, used in the treatment ofPD, such as ropinirole and pramipexole which lack activity at theD1andD5receptors, but resembles that of apomorphine which has greater efficacy inPDthan other dopamine agonists but has suboptimal pharmacokinetic properties.