Enciprazine dihydrochloride

Enciprazine dihydrochloride is an orally active non-benzodiazepine anxiolytic agent. It functions as a 5-HT1A receptor (5-HT1AR) agonist and an α1-adrenergic receptor antagonist. This compound induces changes in drug-induced EEG by decreasing the average power of δ and θ waves while increasing the average power of α and fast β waves. Enciprazine dihydrochloride exhibits anti-aggressive activity with only mild sedative and ataxic effects. It modulates plasma corticosterone levels and activates the hypothalamic-pituitary-adrenal axis. Enciprazine dihydrochloride is applicable in studies related to anxiety disorders, generalized anxiety syndrome, and psychotic conditions.

Enciprazine (oral) dihydrochloride demonstrates anti-aggression and anxiolytic effects in male mice, with an oral ED₅₀ of 1.4 mg/kg observed in the electroshock-induced fighting test. In female rats, a single intraperitoneal dose of Enciprazine (0.3-1.25 mg/kg) slightly increases time spent on open arms in the elevated plus maze, up to 32%, while no activity appears at oral doses of 1.5 to 20 mg/kg in the elevated radial arm maze. Enciprazine (oral) dihydrochloride induces ataxic-sedative effects in mice, with an oral ED₅₀ of 120 mg/kg, having a therapeutic index of 86 compared to its anxiolytic and anti-aggression effects. It enhances barbiturate-induced sedation with an oral ED₅₀ of 46.4 mg/kg in mice, with a therapeutic index of 33 compared to its primary effects. Additionally, it enhances ethanol-induced sedation in mice with an oral ED₅₀ of 45.5 mg/kg, having a therapeutic index of 32.5. Rats exhibit no signs of physical dependence with oral doses up to 2 x 50 mg/kg per day for six days per week over 45 days, as confirmed by the absence of withdrawal symptoms. In male Sprague-Dawley rats, a single intraperitoneal dose of Enciprazine (5 mg/kg) induces statistically significant, time-dependent EEG changes, characterized by reduced δ and θ wave activity and increased α and β₂ wave activity, peaking 30-45 minutes post-injection.