Zolpidem is a potent anticonvulsant in adult and aged mice

Abstract

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.