Pardoprunox (formerly known as SLV-308, DU-126891 or SME-308) is novel & potent dopamine D2/5-HT1A receptor agonist that has the potential for the treatment of Parkinson's disease. Pardoprunox acts by binding to dopamine D(2), D(3), and D(4) receptors and 5-HT(1) (A) receptors and is a partial agonist at dopamine D(2) and D(3) receptors and a full agonist at serotonin 5-HT(1) (A) receptors. SLV308 functioned as a strong but partial D(2) receptor agonist at cloned human dopamine D(2,L) receptors (pEC(50) = 8.0 and pA(2) = 8.4) with a 50% efficacy on forskolin stimulated cAMP accumulation. SLV308 functioned as a partial agonist at human recombinant dopamine D(3) receptors, inducing [(35)S]GTPgammaS binding (intrinsic activity of 67%; pEC(50) = 9.2) and inhibiting the dopamine-induced [(35)S]GTPgammaS binding (pA(2) = 9.0). On forskolin-induced cAMP accumulation at cloned human 5-HT(1) (A) receptors, SLV308 functioned as a full 5-HT(1) (A) receptor agonist, albeit with low potency (pEC(50) = 6.3).

Physicochemical Properties

Molecular Formula	C12H15N3O2
Molecular Weight	233.27
Exact Mass	233.116
Elemental Analysis	C, 61.79; H, 6.48; N, 18.01; O, 13.72
CAS #	269718-84-5
Related CAS #	Pardoprunox hydrochloride; 269718-83-4
PubChem CID	6918525
Appearance	Solid powder
LogP	1.288
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	17
Complexity	302
Defined Atom Stereocenter Count	0
SMILES	O=C1OC2=C(N3CCN(C)CC3)C=CC=C2N1
InChi Key	YVPUUUDAZYFFQT-UHFFFAOYSA-N
InChi Code	InChI=1S/C12H15N3O2/c1-14-5-7-15(8-6-14)10-4-2-3-9-11(10)17-12(16)13-9/h2-4H,5-8H2,1H3,(H,13,16)
Chemical Name	7-(4-methylpiperazin-1-yl)-3H-1,3-benzoxazol-2-one
Synonyms	Pardoprunox; SLV-308; SLV 308; SLV308; DU-126891; DU126891; DU 126891; SME-308; SME308; SME308
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	5-HT1A Receptor ( pEC50 = 6.3 ); D2 Receptor ( pEC50 = 8 ); D3 Receptor ( pEC50 = 9.2 )
ln Vitro	In vitro activity: Pardoprunox (SLV-308) has a 50% efficacy on forskolin-stimulated cAMP accumulation and functions as a strong but partial D2 receptor agonist (pEC50= 8.0 and pA2= 8.4). At human recombinant dopamine D3 receptors, Pardoprunox acts as a partial agonist in the induction of [(35)S]GTPgammaS binding (intrinsic activity of 67%; pEC50=9.2) and antagonized the dopamine induction of [(35)S]GTPgammaS binding (pA2=9.0). On forskolin-induced cAMP accumulation at cloned human 5-HT1A receptors, pardoprunox functions as a full 5-HT1A receptor agonist, albeit with low potency (pEC50=6.3)[1].
ln Vivo	Pardoprunox induces contralateral turning behaviour in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra pars compacta (SNpc) (MED=0.03mg/kg; po). In MPTP-treated common marmosets, Pardoprunox dose-dependently increases locomotor activity (MED=0.03mg/kg; po) and decreases motor disability (MED=0.03mg/kg; po). In contrast Pardoprunox attenuated novelty-induced locomotor activity (MED=0.01mg/kg; po), (+)-amphetamine-induced hyperlocomotion (MED=0.3mg/kg; po) and apomorphine-induced climbing (MED=0.6mg/kg; po) in rodents. Pardoprunox also induces 5-HT1A receptor-mediated behaviours, including flat body posture and lower lip retraction (MED=0.3mg/kg; po). Collectively, these findings demonstrate that Pardoprunox possesses dopamine D2/3 partial agonist effects, 5-HT1A agonist effects and reduces parkinsonism in animal models. functional D2 receptor partial agonist activity and is effective in experimental models predictive of efficacy in PD
Animal Protocol	0.03mg/kg; po Rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra pars compacta (SNpc)
References	[1]. 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 agonist. Synapse. 2006 Dec 15;60(8):599-608. [2]. Double-blind study of pardoprunox, a new partial dopamine agonist, in early Parkinson's disease. Mov Disord. 2010 Apr 30;25(6):738-46. [3]. In vivo effects of pardoprunox (SLV308), a partial D?/D? receptor and 5-HT1A receptor agonist, on rat dopamine and serotonin neuronal activity. Synapse. 2011 Oct;65(10):1042-51.
Additional Infomation	Pardoprunox has been used in trials studying the treatment of Early Stage Parkinson's Disease and Advanced Stage Parkinson's Disease. Pardoprunox is a partial dopamine D2 agonist and noradrenergic agonist with serotonin 5-HT1A agonist properties. Mechanism of Action Pardoprunox binds to dopamine D(2), D(3), and D(4) receptors and 5-HT(1) (A) receptors and is a partial agonist at dopamine D(2) and D(3) receptors and a full agonist at serotonin 5-HT(1) (A) receptors. Pardoprunox combines high potency partial agonism at dopamine D(2) and D(3) receptors with full efficacy low potency serotonin 5-HT(1) (A) receptor agonism and is worthy of profiling in in vivo models of Parkinson's disease.

Solubility Data

Solubility (In Vitro)	DMSO: ~10 mM Water: <1 mg/mL Ethanol: <1 mg/mL
Solubility (In Vivo)	O=C1OC2=C(N3CCN(C)CC3)C=CC=C2N1  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.2869 mL	21.4344 mL	42.8688 mL
	5 mM	0.8574 mL	4.2869 mL	8.5738 mL
	10 mM	0.4287 mL	2.1434 mL	4.2869 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.