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 establi shed in transfected cell lines expressing human D2 or D3 receptors. Th e functional selectivity of agonists markedly differs from their bindi ng selectivity. (+)7-OH-DPAT, pramipexole, quinerolane and PD 128,907, the most D3 receptor-selective compounds in binding studies, were 7,1 5,21 and 54 times more potent, respectively, at the D3 than at the D2 receptor in the functional test. Bromocriptine displayed a 10-fold fun ctional selectivity toward the D2 receptor. The known behavioural acti ons of D3 selective agonists support a role for the D3 receptor in mot or inhibitions, which should be taken into account for the treatment o f motor dysfunctions by dopamine agonists.