engleski

Anticonvulsant and sedative activity of zolpidem in adult and aged mice

Zolpidem is a widely used hypnotic drug known to bind with highest affinity to benzodiazepine sites located on GABA-A receptors containing alpha1 subunit. The pharmacological profile of this drug appears to be different from that of classical benzodiazepines. Unlike benzodiazepines, zolpidem has very pronounced sedative and mild anxiolytic and anticonvulsant properties. Although older people take hypnotic drugs more often than young people, most preclinical studies are performed on adult or young animals, while the studies on aged and old animals are relatively scarce. The aim of this study was to compare the sedative and anticonvulsant effects of zolpidem between adult and aged mice. Sedative activity was assessed by measuring the decreases in locomotor activity. Seizures were produced by an i. v. infusion of picrotoxin or pentylenetetrazole (PTZ). Both compounds are supposed to be non-competitive GABA-A receptor antagonists. The seizure threshold of control vehicle treated aged (13 months) CBA mice was lower than that of adult (3 months) mice, while their locomotor activity was identical. Zolpidem (0.1, 1.0 and 10.0 mg/kg i.p.) produced similar decreases in locomotor activity of adult and aged mice. When given 30 min before the infusion of convulsants was started, zolpidem (1.0 and 10.0 mg/kg) enhanced in adult and aged mice the threshold for PTZ-induced myoclonus, clonic and tonic convulsions, and 10.0 mg/kg enhanced the threshold for picrotoxin-induced clonic and tonic seizures. The anticonvulsant effects obtained by 10.0 mg/kg of zolpidem were of similar intensity in adult and aged mice. Although the sedative effect of zolpidem in mice was the same regardless of age, its anticonvulsant effect obtained by 1.0 mg/kg against PTZ-induced myoclonic and clonic seizures was greater in aged than in adult mice. The results demonstrate strong anticonvulsant properties of zolpidem in both adult and aged mice.

zolpidem; PTZ-induced seizures; sedative activity; age differences

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