A FUNCTIONAL TEST IDENTIFIES DOPAMINE AGONISTS SELECTIVE FOR D3 VERSUS D2 RECEPTORS

THE functional potency of a series of dopamine agonists for increasing mitogenesis, measured by incorporation of [H-3]thymidine, was established in transfected cell lines expressing human D2 or D3 receptors. The functional selectivity of agonists markedly differs from their binding selectivity. (+)7-OH-DPAT, pramipexole, quinerolane and PD 128,907, the most D3 receptor-selective compounds in binding studies, were 7,15,21 and 54 times more potent, respectively, at the D3 than at the D2 receptor in the functional test. Bromocriptine displayed a 10-fold functional selectivity toward the D2 receptor. The known behavioural actions of D3 selective agonists support a role for the D3 receptor in motor inhibitions, which should be taken into account for the treatment of motor dysfunctions by dopamine agonists.