Pardoprunox is a partial agonist of dopamine D2 and D3 receptors (EC50s = 10 and 0.63 nM, respectively) and a full agonist of the serotonin (5-HT) receptor subtype 5-HT1A (EC50 = 501 nM) in radioligand binding assays.1 It is selective for dopamine D2 and D3 and 5-HT1A receptors over a panel of neurotransmitter receptors (Kis = >1,000 nM). Pardoprunox reduces the accumulation of cAMP induced by forskolin in a concentration-dependent manner and blocks quinpirole-induced inhibition of dopamine release (pA2 = 8.5) in rat striatal slices. Pardoprunox increases contralateral turning behavior in a 6-OHDA rat model of Parkinson’s disease (ED50 = 0.03 mg/kg).2 It also reduces hyperlocomotion induced by amphetamine and induces 5-HT1A-mediated flat body posturing and lower lip retraction in rats. Pardoprunox (0.01-0.3 mg/kg) increases locomotor activity in a marmoset model of Parkinson’s disease induced by MPTP in a dose-dependent manner. Formulations containing pardoprunox are under clinical investigation for the treatment of Parkinson’s disease-associated motor fluctuations.3
1.Glennon, J.C., Van Scharrenburg, G., Ronken, E., et al.In vitro characterization of SLV308 (7-[4-methyl-1-piperazinyl]-2(3H)-benzoxazolone, monohydrochloride): A novel partial dopamine D2 and D3 receptor agonist and serotonin 5-HT1A receptor agonistSynapse60(8)599-608(2006) 2.Jones, C.A., Johnston, L.C., Jackson, M.J., et al.An in vivo pharmacological evaluation of pardoprunox (SLV308)—A novel combined dopamine D2/D3 receptor partial agonist and 5-HT1A receptor agonist with efficacy in experimental models of Parkinson's diseaseEur. Neuropsychopharmacol.20(8)582-593(2010) 3.Rascol, O., Brozova, J., Hauser, R.A., et al.Pardoprunox as adjunct therapy to levodopa in patients with Parkinson's disease experiencing motor fluctuations: Results of a double-blind, randomized, placebo-controlled, trialParkinsonism Relat. Disord.18(4)370-376(2012)