Tracazolate

Tracazolate (ICI 136753) is an orally active non-benzodiazepine anxiolytic. Tracazolate significantly enhances the binding of the radioligand ³H-flunitrazepam (³H-FLU) to brain tissue benzodiazepine receptors. Tracazolate enhances the binding of γ-aminobutyric acid (GABA) to its receptors. Tracazolate exhibits anticonvulsant activity. Tracazolate can be used in anxiety-related research^[1][2]. In Vitro:Tracazolate enhances the binding of [³H]flunitrazepam to benzodiazepine receptor sites in mammalian brain tissue^[1].
Tracazolate enhances the binding of [³H]GABA to its receptor sites in mammalian brain tissue^[1].
Tracazolate enhances the binding of [³H]flunitrazepam to brain tissue^[2].
Tracazolate enhances GABA binding to rat brain membrane fractions^[2]. In Vivo:Tracazolate (10-80 mg/kg; i.p.; p.o.; single administration) exhibits dose-dependent anxiolytic activity in rat shock-induced drinking suppression tests, with a relative potency of 1/4 to 1/2 that of Chlordiazepoxide^[1].
At all tested doses, Tracazolate (5-40 mg/kg; i.p.; p.o.; single administration) produces no statistically significant anxiolytic activity in the rat Geller conflict test^[1].
Tracazolate (40-80 mg/kg; p.o.; once daily; for 12 consecutive days) shows no tolerance to its anxiolytic activity after intragastric administration at 40 or 80 mg/kg once daily for 12 consecutive days in rats^[1].
Tracazolate (25-200 mg/kg; oral administration; single dose) exhibits dose-dependent anxiolytic activity in the mouse exploratory conflict test, with a minimum effective dose of 25 mg/kg p.o^[1].
Tracazolate (i.p.; single administration) acts as a weak antagonist against Metrazol- and Bicuculline (HY-N0219)-induced convulsions in mice, with an i.p. ED₅₀ of 27.7 mg/kg and 22.5 mg/kg, respectively^[1].
Tracazolate (oral administration; single dose) impairs the rotarod performance of mice at high doses, with an oral ED₅₀ of 117.1 mg/kg^[1]
Tracazolate (oral administration; single dose) does not impair rotarod performance in rats when administered at doses up to 400 mg/kg via intragastric gavage^[1].
Tracazolate (12.5-100 mg/kg; p.o.; single administration) does not significantly exacerbate ethanol-induced impairment in the rotarod test in mice, even at an intragastric dose as high as 100 mg/kg^[1].
Tracazolate (12.5-50 mg/kg; p.o.; single administration) enhances ethanol-induced sleep duration in mice at oral doses of 25 mg/kg and above, and its minimum effective dose is comparable to that for anxiolytic effects^[1].
Tracazolate (5-10 mg/kg; p.o.; single administration) potentiates the anxiolytic activity of Chlordiazepoxide in a rat model of shock-induced feeding inhibition^[1].
Tracazolate (12.5 mg/kg; intraperitoneal injection; single administration) enhances the anticonvulsant activity of chlordiazepoxide in mice, reducing the ED₅₀ of Chlordiazepoxide by approximately 6-fold^[1].
Tracazolate (20-40 mg/kg; i.p.; single administration) does not increase water intake in non-water-deprived rats, nor does it do so at i.p. doses of 20 or 40 mg/kg, indicating that its anxiolytic activity is independent of drive^[1].