Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zolpidem and diazepam are widely used drugs acting via benzodiazepine binding sites on GABA(A) receptors. While diazepam is non-selective, zolpidem has a high affinity for alpha1-, and no affinity for alpha5-containing receptors. Several studies suggested that behavioral effects of zolpidem might be more similar to classical benzodiazepines than previously thought. To compare the sedative and anticonvulsant properties of these drugs and to evaluate the importance of GABA(A) receptor subunits for development of tolerance during chronic treatment, we tested the effects of acute and repeated administration of zolpidem and diazepam on ambulatory locomotor activity (a measure of sedation) and on the threshold for myoclonic, clonic and tonic seizures in response to i.v. infusion of pentylenetetrazole (PTZ). Both drugs given acutely in doses 0.3, 1 and 3 mg/kg reduced locomotion, and in doses 1 and 3 mg/kg elevated the threshold for PTZ-induced seizures. The effects of zolpidem and diazepam on the tonic seizure threshold were greater than on myoclonus and clonic seizure threshold. Diazepam and zolpidem (3 mg/kg), given 18 or 42 h after repeated drug treatment (10 days, 5 mg/kg, twice daily), decreased the PTZ seizure threshold and increased the locomotor activity as compared to control mice, indicating development of tolerance to their anticonvulsant and sedative effects. After repeated treatment the PTZ seizure threshold was not different between the two drugs, while differences in sedation became larger than after the acute treatment. The results suggest that alpha5-containing GABA(A) receptors are not crucial for the development of sedative and anticonvulsant tolerance.
 ...
PMID:Effects of acute and repeated zolpidem treatment on pentylenetetrazole-induced seizure threshold and on locomotor activity: comparison with diazepam. 1934 34

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.
 ...
PMID:Zolpidem is a potent anticonvulsant in adult and aged mice. 1991 23