Zolpidem is a recently introduced sleep-inducer which is thought to act on the central-type benzodiazepine receptors. This observation is the first report of drug poisoning with this compound. The toxic response was characterized by the development of a profound but short-lasting coma, associated with pin-point pupils and respiratory depression, as observed in a narcotic overdose. These clinical signs were not influenced by the administration of naloxone, but responded dramatically to flumazenil. Some analytical data on zolpidem toxicokinetics are presented.
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References
1.
Nicholson AN & Pascoe PAHypnotic activity of an imidazopyridazine (zolpidem). British Journal of Clinical Pharmacology1986; 21: 205-11.
2.
Arbilla S., Allen J., Wick A. & Langer SZHigh affinity 3H-zolpidem binding sites in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors. EuropeanJournal of Pharmacology1986; 130: 257-63.
3.
Guinebault P. , Dubruc C., Hermann P. & Thenot JPHigh-performance chromatographic determination of zolpidem, a new sleep inducer, in biological fluids with fluorometric detection . Journal of Chromatography1986; 383: 206-11.
4.
Debailleul G. , Abi Khalil F. & Lheureux P.HPLC quantification of zolpidem and prothipendyl in a voluntary intoxication. Journal of Analytical Toxicology (submitted).
5.
Arbilla S., Allen J., Wick A. & Langer SZHigh affinity 3H-zolpidem binding in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors. EuropeanJournal of Pharmacology1986; 130: 257-63.
6.
Depoortere H. , Sivkovic B., Lloyd KG et al. Zolpidem, a novel non-benzodiazepine hypnotic. I. Neuropharmacological and behavioural effects. Journal of Pharmacology and Experimental Therapy1986; 237: 649-58.
7.
Arbilla S., Depoortere H., George P. & Langer SZPharmacological profile of the imidazopyridine zolpidem at benzodiazepine receptors and electrocorticogram in rats. Naunym-SchmiedebergsArchives of Pharmacology1985; 330: 248-51.
8.
Wheatley, D.Zolpidem: a new imidazopyridine hypnotic. Psychopharmacology Bulletin1989; 25: 124-7.
9.
Höjer J., Baehrendtz S. & Gustafsson L.Benzodiazepine poisoning: experience of 702 admissions to an intensive care unit during a 14-year period. Journal of Internal Medicine1989; 226: 117-23.
10.
Olson KR, Yin L., Osterlo J. & Tani A.Coma caused by trivial triazolam overdose. American Journal of Emergency Medicine1985; 3: 210-11.
11.
Forrest Arw , Marsh I., Bradshaw C. & Braich SKFatal temazepam overdose. Lancet1986; 2: 226.
12.
Martin CD & Chan SCDistribution of temazepam in tissue and body fluids in lethal overdose. Journal of Analytical Toxicology1986; 10: 77-8.
13.
Sunter JP, Bal TS & Cowan WKThree fatal cases of triazolam poisoning. British Medical Journal1988; 297: 719.
14.
Bell EBThe use of naloxone in the treatment of diazepam poisoning. Journal ofPediatrics1975; 87: 803-4.
15.
Moss IMNaloxone reversal of non narcotic induced coma. Journal of the American College of Emergency Physicians1973; 1: 46-8.
16.
Jordan C., Tech B., Lehane JR & Jones JBRespiratory depression following diazepam: reversal with high-dose naloxone . Anesthesiology1980; 58295-8.
17.
Christensen KN & Huttel M.Naloxone does not antagonize diazepam induced sedation. Anesthesiology1979; 51: 187.
18.
Forster A., Morel D., Bachmann M. & Gemperle M.Respiratory depressant effects of different doses of midazolam and lack of reversal with naloxone. A double-blind randomized study. Anaesthetics Analgesics1983; 62: 920-4.
19.
Lheureux P. & Askenasi R.Double-blind study of Anexate in benzodiazepine intoxication. European Journal of Anaesthesiology1988; S2: 300-4.
20.
Naef MM, Foster A., Nahory A., Danjou P. & Rosenzweig P.Flumazenil antagonizes the sedative action of zolpidem, a new imidazopyridine hypnotic. Anesthesiology1989; 71: A298.
21.
Lheureux P. & Askenasi R.Agonism and antagonism at the benzodiasepine-receptor: a new concept for a new approach of common drug poisoning. Acta Anaesthesia (Belgium)1989; 40: 23-8.
22.
Thenot JP, Hermann P., Durant A. et al. Pharmacokinetics and metabolism of zolpidem in various animal species and in humans. In: Imidazopyridines in Sleep Disorders , ed JP Sauvagnet, SZ Langer and PL Morselli, LERS monograph series vol. 6. pp139-153. New York: Raven Press, 1988.
