Dexpramipexole (also known as KNS-760704, R-(+)-Pramipexole and (R)-Pramipexole), an enantiomer of pramipexole, is a dopamine agonist of the non-ergoline class with the potential for the treatment of amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig’s disease). It continuously and significantly reduces eosinophils in peripheral blood. In studies involving human subjects, dexpramipexole—a low molecular weight, water-soluble, orally bioavailable, renally excreted drug with linear pharmacokinetics—has proven to be well tolerated. The enantiomer of pramipexole, KNS-760704, has been demonstrated to significantly protect neurons under stress and enhance mitochondrial function.

Physicochemical Properties

Molecular Formula	C10H19CL2N3S
Molecular Weight	284.2490
Exact Mass	283.068
Elemental Analysis	C, 42.26; H, 6.74; Cl, 24.94; N, 14.78; S, 11.28
CAS #	104632-27-1
Related CAS #	Pramipexole dihydrochloride; 104632-25-9; Pramipexole; 104632-26-0; Pramipexole dihydrochloride hydrate; 191217-81-9; Dexpramipexole; 104632-28-2; 908244-04-2 (HCl hydrate)
PubChem CID	46174453
Appearance	White to off-white solid powder
LogP	3.507
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	17
Complexity	188
Defined Atom Stereocenter Count	1
SMILES	Cl[H].Cl[H].S1C(N([H])[H])=NC2=C1C([H])([H])[C@@]([H])(C([H])([H])C2([H])[H])N([H])C([H])([H])C([H])([H])C([H])([H])[H]
InChi Key	QMNWXHSYPXQFSK-XCUBXKJBSA-N
InChi Code	InChI=1S/C10H17N3S.2ClH/c1-2-5-12-7-3-4-8-9(6-7)14-10(11)13-8;;/h7,12H,2-6H2,1H3,(H2,11,13);2*1H/t7-;;/m1../s1
Chemical Name	(6R)-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine;dihydrochloride
Synonyms	Dexpramipexole dihydrochloride; KNS-760704; KNS760704; KNS 760704; R-Pramipexole; 104632-27-1; DEXPRAMIPEXOLE DIHYDROCHLORIDE; Dexpramipexole (dihydrochloride); SND 919CL2x; (R)-Pramipexole Dihydrochloride; KNS 760704; CHEMBL3216394; I9038PKO43;
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	Dopamine Receptor
ln Vitro	Dexpramipexole has been found to be neuroprotective and is currently being studied for the treatment of amyotrophic lateral sclerosis (ALS). Dexpramipexole reduces mitochondrial reactive oxygen species (ROS) production, inhibits activation of apoptotic pathways, and increases cell survival against various neurotoxins and beta-amyloid neurotoxicity. Dexpramipexole has much lower dopamine agonist activity than the S-(-) isomer.
ln Vivo	Dexpramipexole increased mitochondrial ATP production in cultured neurons or glia and reduces energy failure, prevents intracellular Ca2+ overload and affords cytoprotection when cultures are exposed to OGD. This compound also counteracted ATP depletion, mitochondrial swelling, anoxic depolarization, loss of synaptic activity and neuronal death in hippocampal slices subjected to OGD. Post‐ischaemic treatment with dexpramipexole, at doses consistent with those already used in ALS patients, reduced brain infarct size and ameliorated neuroscore in mice subjected to transient or permanent MCAo[2].
Cell Assay	Neuronal/astrocytes cultures were prepared from rat embryos (E‐17/E‐19) or pups (P‐1/P‐2), as reported (Chiarugi et al., 2003). Briefly, the cerebral cortex was minced using medium stock (MS) (Eagle's minimal essential medium with Earle's salts, glutamine‐ and NaHCO3‐free, NaHCO3 38 mM, glucose 22 mM, penicillin 100 U·mL−1 and streptomycin 100 µg·mL−1) and then incubated for 10 (neurons) and 45 min (astrocytes) at 37°C in MS supplemented with 0.25% trypsin and 0.05% DNase. Enzymic digestion was terminated by incubation (10 min at 37°C) in MS supplemented with 10% heat‐inactivated horse serum (HIHS) and 10% FBS. Following tissue mechanical disruption, cells were counted and plated. For mixed cortical cell cultures, neurons were re‐suspended at a density of 4 × 105 cells·mL−1 and plated in 15 mm multiwell on a layer of confluent astrocytes using MS supplemented with 10% HIHS, 10% FBS and 2 mM glutamine. After 4–5 days in vitro, non‐neuronal cell division was halted by the application of 3 µM cytosine arabinoside for 24 h. Cell cultures were subjected to oxygen‐glucose deprivation (OGD) in the presence or absence of DEX in a serum‐ and glucose‐free medium saturated with 95% N2 and 5% CO2. Following 2 h of incubation at 37°C in an anoxic chamber, the cultures were transferred to oxygenated serum‐free medium (75% Eagle's minimal essential medium; 25% Hank's balanced salt solution; 2 mM l‐glutamine; 3.75 µg·mL−1 amphotericin B; and 5 mg·mL−1 glucose) and returned to normoxic conditions in the presence or absence of DEX. Propidium iodide (PI) fluorescence was evaluated 24 h later[2].
Animal Protocol	Acute hippocampal slice preparation and OGD exposure[2] Acute hippocampal slices were prepared from male SD rats (Charles River, Calco, Italy, 150–200 g) as described (Pugliese et al., 2009). Hippocampi were removed and placed in ice‐cold oxygenated artificial CSF of the following composition (mM): NaCl 125, KCl 3, NaH2PO4 1.25, MgSO4 1, CaCl2 2, NaHCO3 25 and D‐glucose 10. Slices of 400 mm were prepared and kept in oxygenated aCSF for at least 1 h at RT. A single slice was then placed on a nylon mesh, completely submerged in a small chamber (0.8 mL) and superfused with oxygenated aCSF (31–32°C) at a constant flow rate of 1.5–1.8 mL·min−1. Under OGD condition, the slice was superfused with aCSF without glucose and gassed with 95%N2–5% CO2. This caused a drop in pO2 in the recording chamber from ~500 mmHg (normoxia) to a range of 35–75 mmHg (after 7 min OGD). (Pugliese et al., 2003) At the end of the ischaemic period, the slice was again superfused with normal, glucose‐containing, oxygenated aCSF. Control slices were not subjected to OGD or drug treatment but were incubated in oxygenated aCSF for identical time intervals. Hippocampal slices were (i) incubated for at least 1 h before electrophysiological recordings in the presence of DEX, which was maintained throughout the experiments or (ii) superfused in the presence of DEX at least 30 min before and after OGD application.
Toxicity/Toxicokinetics	Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of pramipexole during breastfeeding, but it suppresses serum prolactin and may interfere with breastfeeding. An alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information in nursing mothers was not found as of the revision date. Pramipexole lowers serum prolactin.[1] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
References	[1]. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Jan;14(1):44-51. [2]. Br J Pharmacol. 2018 Jan; 175(2): 272–283.
Additional Infomation	The (R)-(+) enantiomer of PRAMIPEXOLE. Dexpramipexole has lower affinity for DOPAMINE RECEPTORS than pramipexole.

Solubility Data

Solubility (In Vitro)

H2O : ~100 mg/mL (~351.80 mM) DMSO : ≥ 100 mg/mL (~351.80 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (7.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (351.80 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.5180 mL	17.5901 mL	35.1803 mL
	5 mM	0.7036 mL	3.5180 mL	7.0361 mL
	10 mM	0.3518 mL	1.7590 mL	3.5180 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.