Dexpramipexole (dihydrochloride)

Dexpramipexole ((R)-Pramipexole) dihydrochloride is an orally active, blood-brain barrier permeable mitochondrial protective agent. Dexpramipexole dihydrochloride upregulates the expression of Parkin, PINK1, GPX4 and FSP1; binds to mitochondrial F1/Fo-ATP synthase; blocks the Na_v1.8 sodium channel; and inhibits the activation of the NLRP3 inflammasome. Dexpramipexole dihydrochloride induces mitophagy, inhibits ferroptosis, pyroptosis, apoptosis, neuroinflammation and eosinophilopoiesis; maintains mitochondrial function and redox homeostasis; reduces reactive oxygen species production; and decreases myocardial infarct size. Dexpramipexole dihydrochloride is applicable to studies on eosinophilic asthma, myocardial ischemia/reperfusion injury, sepsis-associated encephalopathy, analgesia, and more^{[1][2][3][4][5][6]}. In Vitro:Dexpramipexole (5-200 μM; 24 h) dihydrochloride shows no cytotoxicity to primary cardiomyocytes isolated from neonatal rats at concentrations below 100 μM, while the compound at 200 μM reduces cell viability^[1].
Dexpramipexole (2-50 μM) dihydrochloride protects primary neonatal rat cardiomyocytes against hypoxia/reoxygenation (H/R)-induced injury by enhancing cell viability and reducing LDH release^[1].
Dexpramipexole (2-50 μM) dihydrochloride upregulates the expression level of PINK1 protein in primary cardiomyocytes from neonatal rats treated with H/R^[1].
Dexpramipexole dihydrochloride protects primary cardiomyocytes from neonatal rats against H/R-induced mitochondrial dysfunction by reducing mPTP opening, decreasing ROS production and restoring mitochondrial membrane potential^[1].
Dexpramipexole dihydrochloride enhances ATG7-dependent mitophagy in primary neonatal rat cardiomyocytes subjected to H/R, which is characterized by increased formation of mitophagosomes, enhanced autophagic mitochondrial sequestration, and improved mitochondrial clearance^[1].
Dexpramipexole dihydrochloride activates PINK1 and Parkin and promotes mitochondrial fission in primary neonatal rat cardiomyocytes exposed to H/R^[1].
Dexpramipexole dihydrochloride protects primary cardiomyocytes from neonatal rats against H/R injury by upregulating PINK1- and Parkin-dependent mitophagy^[1].
Dexpramipexole (10 μM; 5 min) dihydrochloride inhibits tetrodotoxin-resistant sodium currents in primary cultured rat dorsal root ganglion neurons with an IC₅₀ of 294.4 nM, and does not alter the voltage-dependent activation or inactivation properties of the channels^[5].
Dexpramipexole (10 μM) dihydrochloride selectively inhibits Nav1.8-mediated sodium currents in primary cultured dorsal root ganglion neurons from wild-type mice^[5]. In Vivo:Dexpramipexole (1 mg/kg; single administration) dihydrochloride alleviates myocardial ischemia/reperfusion injury in male C57BL/6 mice by reducing infarct size, restoring cardiac function, decreasing serum levels of myocardial injury biomarkers, and enhancing PINK1/Parkin-dependent mitophagy^[1].
Dexpramipexole (5-20 mg/kg; i.p., once daily for 14 consecutive days) dihydrochloride improves survival rate, body weight gain, spontaneous activity, motor coordination and forelimb muscle strength, reduces hematoma volume, alleviates white matter injury, decreases iron and ROS accumulation, and inhibits ferroptosis by upregulating GPX4 and FSP1 in mice with intracerebral hemorrhage^[2].
Dexpramipexole (3 mg/kg; i.p.; once daily for 6 consecutive days) dihydrochloride improves lipopolysaccharide (LPS)-induced cognitive impairment in sepsis-associated encephalopathy (SAE), preserves the morphology and function of hippocampal mitochondria in mice, and inhibits mitochondria-mediated pyroptosis and apoptosis^[3].
Dexpramipexole (3-20 mg/kg; 20-140 μg/20 μL; p.o.; i.p.; hind paw s.c.; single administration) dihydrochloride exerts effective analgesic effects in various mouse models of nociceptive pain (e.g., inflammatory pain, visceral pain) and neuropathic pain (e.g., chemotherapy-induced pain, nerve compression pain, diabetic neuropathic pain)^[5].