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 [3H]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.
Sautel
F
F
Unité de Neurobiologie et Pharmacologie, Centre Paul Broca de l'INSERM, Paris, France.
Griffon
N
N
Lévesque
D
D
Pilon
C
C
Schwartz
J C
JC
Sokoloff
P
P
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015259:Dopamine Agents / Q000494:pharmacology*; D006801:Humans; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3
C493593:DRD3 protein, human; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3