Dopamine receptor agonists

Of the two major classes of DA receptors, D1 and D2, it is generally accepted that D1 receptors function in the direct pathway in the basal ganglia whereas the D2 receptors function in a parallel indirect pathway. Thus, D1 receptor activation facilitates movement whereas D2 receptor activation inhibits movement. DA receptor agonists used in the clinic comprise two broad chemical classes: the non-ergolines, including apomorphine 58, pramipexole 60, and ropinirole 61; and ergolines, bromocriptine 59 and pergolide 62. Pramipexole is a D2 selective, full agonist with ropinirole having a similar profile being also active at D3 receptors. Apomorphine binds with highest affinity to the D4 receptor but also interacts with D1 and D2 receptors. While newer D1 agonists like ABT-431 63 failed to show improved benefit in Phase II trials, additional D2 agonists are in clinical trials and include the partial D2 agonist, SLV-308, and the D2 agonist, rotigotine.

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