Enciprazine (dihydrochloride)

Enciprazine dihydrochloride is an orally active non-benzodiazepine anxiolytic. Enciprazine dihydrochloride acts as an agonist of 5-HT₁A receptor (5-HT₁AR) and an antagonist of α₁-adrenergic receptor (α1-adrenergic receptor) . Enciprazine dihydrochloride induces drug-related electroencephalogram changes by reducing the average power of δ waves and θ waves, and increasing the average power of α waves and fast β waves. Enciprazine dihydrochloride exhibits anti-aggressive activity, with only weak sedative and ataxic effects. Enciprazine dihydrochloride regulates plasma corticosterone levels and activates the hypothalamic-pituitary-adrenal axis. Enciprazine dihydrochloride can be used in research related to anxiety disorders, generalized anxiety syndrome and psychosis^[1][2][3]. In Vivo:Enciprazine (p.o.) dihydrochloride exhibits anti-aggression and anxiolytic activities in male mice, with an oral ED₅₀ of 1.4 mg/kg in the electroshock-induced fighting test^[1].
Enciprazine (0.3-1.25 mg/kg; i.p.; single administration) dihydrochloride mildly prolongs the time female rats spend in the open arms in the elevated plus maze test, with a maximum increase of up to 32%; however, no activity is observed at oral doses of 1.5 to 20 mg/kg in the elevated radial arm maze test^[1].
Enciprazine (p.o.) dihydrochloride exhibits ataxic sedative effects in mice, with an oral ED₅₀ of 120 mg/kg and a therapeutic index of 86 relative to its anxiolytic and anti-aggressive activities^[1].
Enciprazine (p.o.) dihydrochloride potentiates hexobarbital-induced sedation in mice, with an oral ED₅₀ of 46.4 mg/kg, and its therapeutic index reaches 33 relative to its anxiolytic and anti-aggressive activities^[1].
Enciprazine (p.o.) dihydrochloride potentiates ethanol-induced sedation in mice, with an oral ED₅₀ of 45.5 mg/kg and a therapeutic index of 32.5 relative to its anxiolytic and anti-aggressive activities^[1].
Enciprazine (25-50 mg/kg; p.o.; twice daily; administered 6 days per week for 45 days) dihydrochloride shows no tendency toward physical dependence in rats at oral doses up to 2 × 50 mg/kg per day, as evidenced by the absence of withdrawal symptoms following 45 days of chronic administration^[1].
Enciprazine (5 mg/kg; i.p.; single administration) dihydrochloride induces statistically significant, time-dependent electroencephalogram (EEG) changes in freely moving male Sprague-Dawley rats, characterized by decreased δ and θ wave activities and increased α and β₂ wave activities, with the peak effect occurring 30-45 minutes after injection^[2].