Drofenine

Drofenine (Cycloadiphene; Hexahydroadiphenine) is an brain-penetrant antispasmodic agent. Drofenine is a Kv2.1 channel inhibitor with human IC₅₀ of 9.53 μM. Drofenine is a butyrylcholinesterase (BChE) inhibitor with K_i of 0.003 mM, and is a TRPV3 activator. Drofenine blocks Kv2.1-dependent potassium efflux, inhibits Kv2.1/JNK/NF-κB and IkBa/NF-kB signaling, suppresses Kv2.1 mRNA/protein expression. Drofenine suppresses oligomeric Aβ-induced microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation, improves cognitive impairment, promotes neurite outgrowth. Drofenine induces calcium influx in keratinocytes and exert cytotoxicity against keratinocytes. Drofenine ameliorates diabetic peripheral neuropathy -like pathology. Drofenine can be used for the researches of Alzheimer's disease, diabetic peripheral neuropathy and smooth muscle spasm^[1][2][3][4]. In Vitro:Drofenine (10 μM; 0.5 h) suppresses oligomeric Aβ (o-Aβ)-enhanced Kv2.1-dependent outward potassium current and density in CHO-Kv2.1 cells by blocking o-Aβ-induced delays in Kv2.1 channel inactivation^[1].
Drofenine (5-20 μM; 30 min) inhibits membrane potential in CHO-Kv2.1 cells without affecting normal CHO cells^[2].
Drofenine (5-20 μM) does not reduce the viability of CHO-Kv2.1 cells^[2].
Drofenine (1-10 μM) potently inhibits Kv2.1 channel currents in CHO-Kv2.1 cells with an IC₅₀ of 9.53 μM^[2].
Drofenine (1-10 μM) shows minimal inhibition of Kv2.2 channel currents in CHO-Kv2.2 cells at concentrations that effectively inhibit Kv2.1, indicating selectivity for Kv2.1^[2].
Drofenine (0.01-0.1 mM) acts as a pure competitive inhibitor of purified human serum butyrylcholinesterase, with a K_i value of 0.003 mM^[3].
Drofenine (30-1000 μM) acts as a selective agonist of human TRPV3 in TRPV3-overexpressing HEK-293 cells, activating calcium flux with an EC₅₀ of 207 μM without activating TRPA1, TRPM8, TRPV1, TRPV2, or TRPV4 at concentrations up to 1000 μM^[4].
Drofenine (30-1000 μM) acts as a potent agonist of endogenous TRPV3 in HaCaT human keratinocytes, inducing calcium flux with an EC₅₀ of 605 μM^[4].
Drofenine (10-1000 μM; 24 h) is cytotoxic to HaCaT human keratinocytes after 24 h of incubation, with an LC₅₀ of 230 μM^[4]. In Vivo:Drofenine (10 mg/kg/day; i.p.; daily; 8 weeks) ameliorates cognitive impairment, neuroinflammation, tauopathy, synaptic dysfunction, and neuronal loss in 5xFAD Alzheimer's disease mice by inhibiting the Kv2.1/JNK/NF-κB pathway, with no observable hepatotoxicity or nephrotoxicity^[1].
Drofenine (10-20 mg/kg; 4 total doses; Weeks 7, 8, 9, 10 post-STZ injection) suppresses Kv2.1 expression and function in DRG tissue, promotes DRG neuron neurite outgrowth, and ameliorates motor and sensory deficits in STZ (HY-13753)-induced type 1 DPN mice via Kv2.1 inhibition^[2].
Drofenine (10-20 mg/kg; 4 total doses; Weeks 1, 2, 3, 4 of study period) suppresses Kv2.1 expression and function in DRG tissue, promotes DRG neuron neurite outgrowth, and ameliorates motor and sensory deficits in spontaneous type 2 db/db DPN mice^[2].