Zolpidem is a widely used
hypnotic drug acting via
benzodiazepine binding sites on
GABA(A) receptors. Several studies suggested that
zolpidem might have better
anticonvulsant potency than previously thought. To compare the
sedative and
anticonvulsant potency of this drug, we studied in male mice the influence of
zolpidem (0.1-10 mg/kg i.p.) on ambulatory locomotor activity (a measure of sedation) and on the threshold for
myoclonus, clonic and
tonic seizures, as well as death, in response to i.v. infusion of
pentylenetetrazole (PTZ, 4.4 mg/min). Because older people take
zolpidem more often than young people and have a higher incidence of
epilepsy, we also compared the
sedative and
anticonvulsant properties of low doses of this drug (0.1 and 1 mg/kg i.p.) between adult (3 months) and aged (13 months) mice.
Zolpidem in doses of 0.3-10 mg/kg decreased locomotion, as quantified by recording interruptions of infrared beams during 10 min, and in doses of 1-10 mg/kg increased the threshold for PTZ-induced
seizures and death. The effect of
zolpidem against
tonic seizures was greater than against two other seizure components and death. In control aged mice the threshold for PTZ-induced
myoclonus,
clonic seizures and death was lower than in adult mice, while the locomotor activity was not different. In adult and in aged mice
zolpidem in a dose of 1 mg/kg decreased locomotion and elevated the threshold for PTZ-induced
seizures and death. Neither of these effects was age-dependent. The results suggest that in addition to strong
sedative activity
zolpidem has potent
anticonvulsant properties.