Zolpidem (Stilnox), an imidazopyridine derivative, is a strong sedative with minor myorelaxant and anticonvulsant properties which exhibits high-affinity binding at a benzodiazepine-receptor subtype. Although the structure of zolpidem differs from the benzodiazepines, the acute toxicity of zolpidem has generally been compared to triazolam (Halcion) and midazolam (Dormicum). 5 years after introduction of zolpidem to the Swiss market we have therefore retrospectively analyzed 91 well documented cases of acute zolpidem intoxication reported to the Swiss Toxicological Information Center. Furthermore, 54 single-drug poisonings with zolpidem were compared with 53 triazolam and 55 midazolam intoxications observed over the same time period. 0.01-0.02 g of zolpidem is the recommended therapeutic dose. But only mild symptoms were observed in acute single-drug poisonings with zolpidem up to 0.6 g. Patients mainly suffered from somnolence. Only one anorectic patient became comatose after ingestion of 0.6 g zolpidem. The acute toxicity of zolpidem was markedly less pronounced than that of the short-acting benzodiazepines triazolam and midazolam. With forty-fold the therapeutic dose no severe symptoms occurred in patients with zolpidem single-drug poisonings, while coma was encountered in 4 cases with triazolam (11% of patients) and 4 cases with midazolam (10%). While only the patient mentioned above was reported to be comatose after overdosing with zolpidem, 6 (11%) and 8 (15%) comatose patients were observed in triazolam and midazolam single-drug poisonings, respectively. On the other hand, in combined intoxications with other CNS active drugs or ethanol a zolpidem dose as low as 0.1-0.15 s induced coma in some patients, even if the amount of the additionally ingested drugs in itself would not have caused a comatose state. Flumazenil (Anexate) was an effective antidote in mono- and combined intoxications involving zolpidem. In conclusion, our results indicate that zolpidem single-drug poisonings are generally benign and require no specific therapeutic measures. In combined intoxications, however, patients may develop coma at relatively low zolpidem doses and should therefore be monitored for approximately 24 hours. If necessary, disturbances of consciousness can be successfully treated with flumazenil.
[Show abstract][Hide abstract] ABSTRACT: The main inhibitory neurotransmitter receptor of the brain, the gamma-aminobutyric acid type A receptor (GABA[A]), mediates the actions of several classes of clinically important drugs, such as benzodiazepines, barbiturates and general anaesthetics. This review summarizes the current knowledge on how classical benzodiazepines and novel nonbenzodiazepine compounds act on the benzodiazepine site of GABA(A) receptors and on their clinical pharmacology related to anxiolytic, sedative, hypnotic and cognitive effects or side-effects. Partial agonism, receptor subtype selectivity and novel binding sites are discussed as possible strategies to develop new drugs with fewer adverse effects than are seen in the clinical use of benzodiazepines.
Annals of Medicine 09/1997; 29(4):275-82. DOI:10.3109/07853899708999348 · 3.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new method is described for the qualitative and quantitative analysis of midazolam, a short-acting 1,4-imidazole benzodiazepine, in human plasma. It involves a plasma deproteinization step, solid-phase microextraction (SPME) of midazolam using an 85-microm polyacrylate fiber, and its detection by gas chromatography/mass spectrometry (GC/MS) in selected ion monitoring (SIM) mode, using pinazepam as internal standard. The assay is linear over a midazolam plasma range of 1.5-300 ng/mL, relative intra- and inter-assay standard deviations at 5 ng/mL are below 7%, and the limit of detection is 1 ng/mL. The method is simple, fast and sufficiently sensitive to be applied in clinical and forensic toxicology as well as for purposes of therapeutic drug monitoring.
Rapid Communications in Mass Spectrometry 12/2001; 15(24):2497-501. DOI:10.1002/rcm.536 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Zolpidem is a nonbenzodiazepine hypnotic with a favorable adverse effect profile. There are single reports of respiratory decompensation associated with zolpidem overdose. We report a case ofa young woman with depression who developed deep coma with respiratory failure and a loss of brainstem reflexes as a result of zolpidem overdose. Supportive management led to a complete recovery of neurologic function. Acute zolpidem overdose should be considered in the differential diagnosis of coma with absent brainstem reflexes.
American journal of therapeutics 01/2009; 17(5):e172-4. DOI:10.1097/MJT.0b013e318188bdca · 1.13 Impact Factor
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