Pardoprunox(SLV-308) is a novel partial dopamine D2 and D3 receptor agonist and serotonin 5-HT1A receptor agonist; D2 (pKi = 8.1) and D3 receptor (pKi = 8.6) partial agonist (IA = 50% and 67%, respectively) and 5-HT1A receptor (pKi = 8.5) full agonist (IA = 100%); also binds to D4 (pKi = 7.8), α1-adrenergic (pKi = 7.8), α2-adrenergic (pKi = 7.4), and 5-HT7 receptors (pKi = 7.2) with lower affinity. IC50 value: Target: in vitro: SLV308 acted as a potent but partial D(2) receptor agonist (pEC(50) = 8.0 and pA(2) = 8.4) with an efficacy of 50% on forskolin stimulated cAMP accumulation. At human recombinant dopamine D(3) receptors, SLV308 acted as a partial agonist in the induction of [(35)S]GTPgammaS binding (intrinsic activity of 67%; pEC(50) = 9.2) and antagonized the dopamine induction of [(35)S]GTPgammaS binding (pA(2) = 9.0). SLV308 acted as a full 5-HT(1) (A) receptor agonist on forskolin induced cAMP accumulation at cloned human 5-HT(1) (A) receptors but with low potency (pEC(50) = 6.3) [1]. in vivo: Unified PD Rating Scale (UPDRS)-Motor score was improved in pardoprunox-treated patients (overall mean dose 23.8 mg/d; -7.3 points), as compared with placebo (-3.0 points; P = 0.0001), from baseline to end point. At end point, there were more responders (> or = 30% reduction in UPDRS-Motor score) in the pardoprunox group (50.7%) than in the placebo group (15.7%; P < 0.0001) [2]. Surprisingly in the SNc, pardoprunox (10 μg kg 1, i.v.) either partially or fully suppressed the firing activity in two separate populations of DA neurons. Finally, in the DRN, pardoprunox (5-40 μg kg-1, i.v.) completely suppressed the firing activity of 5-HT neurons. Moreover, the selective 5-HT(1A) receptor antagonist WAY-100,635 prevented and reversed the effects of pardoprunox [3].