Zolpidem
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| Non-proprietary name | Zolpidem | ||||||||||||
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N , N -dimethyl-2- (6-methyl-2- p -tolylimidazo [1,2- a ] pyridin-3-yl) acetamide ( IUPAC ) |
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| Brief description |
White solid |
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| Physical state |
firmly |
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| Melting point |
196 ° C (zolpidem) |
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| pK s value |
6.2 |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||
Zolpidem is a drug that is used in sleeping pills or sleeping pills . The substance is structurally an imidazopyridine derivative with a spectrum of activity similar to that of benzodiazepines and, along with zopiclone and zaleplon, is one of the Z-drugs . Zolpidem usually has a very short half-life (2-3 hours) and no pharmacologically active metabolites . In isolated cases, however, much longer half-lives have been observed (up to 10 hours). It is currently the most prescribed sleep aid in the US and Europe. Zolpidem is quickly and easily absorbed by the body, the maximum plasma level is reached after about two hours. In Germany, for example, the prescription of drugs containing zolpidem is legally restricted, primarily because of the risk of addiction .
pharmacology
Zolpidem acts as a positive allosteric modulator on GABA A receptors . It binds to the high-affinity benzodiazepine binding site of this ion channel in the extracellular domain . It binds to ternary receptors at the interface α1 + γ2 - and thereby selectively to the alpha1 subunit . Zolpidem has sedating , muscle relaxing and anticonvulsant effects. It makes falling asleep easier, the duration of sleep is extended. The sleep architecture does not seem to be significantly influenced by zolpidem at low doses. At higher doses, sleep changes are comparable to those caused by benzodiazepines.
23 clinical reports and six studies from 15 years prove the recovery effects of subsedative-dosed zolpidem in brain damage caused by stroke, trauma and hypoxia , such as unexpected waking up from a coma and improvement in stroke symptoms . Waking coma patients were temporarily responsive after taking the drug and reacted to their environment. Unlike previously known GABAergics, zolpidem acts at the α1 + α1 - interface of binary GABA A receptors.
application
Zolpidem is approved in Germany for the short-term treatment of sleep disorders and is used as tartrate salt (zolpidem tartrate) in the form of film-coated tablets of 5 mg or 10 mg.
Due to the high doses required for an anticonvulsant and muscle-relaxing effect and the associated side effects , zolpidem is not used for these indications.
Contraindications
Zolpidem must not be used with pathological muscle weakness ( myasthenia gravis ), with severe breathing problems, with repeated interruption of breathing during sleep ( sleep apnea syndrome ), with severe liver damage and also not in children and adolescents under 18 years of age.
Side effects and restrictions on use
The spectrum of side effects is similar to that of the benzodiazepines. As with these, in addition to fatigue, dullness, headaches and visual disturbances, temporary memory gaps ( anterograde amnesias ), “paradoxical reactions” (restlessness, irritability, aggressiveness) and other behavioral disorders as well as hallucinations and delusions can occur; the risk of the latter occurring is increased especially at higher doses and in elderly patients.
As to be expected from the relationship with the benzodiazepine group, rebound phenomena , tolerance development , physical and psychological dependencies , and withdrawal symptoms upon termination of therapy are possible despite the short plasma half-life . For this reason, it should not be prescribed for more than a few days. The risk of addiction is increased in patients with pre-existing addiction disorders. In combination with alcohol or other sedative substances (especially benzodiazepines), an increase in the effect is to be expected, which is why the maximum daily dose of 10 mg (adults) and 5 mg (elderly and weakened patients) should not be exceeded. Women in particular are affected due to gender-specific differences in the breakdown of zolpidem via the cytochrome P450 system of the liver, since relevant blood levels may still exist the morning after ingestion. The US Food and Drug Administration ( FDA ) recommends not driving or engaging in other activities that also require full mental alertness in the morning after taking zolpidem, even in low doses (6.25 mg) because of the risk of delayed reactions. These recommendations were confirmed by the MHRA in 2014 .
Legal status
According to Appendix III of the Narcotics Act (BtMG), zolpidem is a prescription drug in Germany . This does not apply to preparations for oral use which, without another substance in Annexes I to III BtMG, contain only up to 8.5 mg zolpidem (calculated as base) per divided form and can therefore be prescribed on a non-official prescription form.
In Austria and Switzerland, zolpidem requires a prescription.
Trade names
Monopreparations : Ambien (USA), Bikalm (D), Ivadal (A), Mondeal (A), Stilnox (D, CH, I, F, E, GB, CZ), Zoldem (D, A), Zoldorm (CH) , numerous generics (D, A, CH)
Web links
Individual evidence
- ↑ a b c d data sheet zolpidem at Sigma-Aldrich , accessed on June 16, 2011 ( PDF ).
- ^ The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 1754, ISBN 978-0-911910-00-1 .
- ↑ Entry on zolpidem in the ChemIDplus database of the United States National Library of Medicine (NLM) .
- ↑ a b Entry on zolpidem in the DrugBank of the University of Alberta .
- ^ Salvà P, Costa J: Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications . In: Clin Pharmacokinet . 29, No. 3, September 1995, pp. 142-53. doi : 10.2165 / 00003088-199529030-00002 . PMID 8521677 .
- ↑ Sutton JA, Clauss RP: A review of the evidence of zolpidem efficacy in neurological disability after brain damage due to stroke, trauma and hypoxia: A justification of further clinical trials . In: Brain Inj . 31, No. 8, 2017, pp. 1019-1027. doi : 10.1080 / 02699052.2017.1300836 . PMID 28534652 .
- ↑ Che Has AT, Absalom N, van Nieuwenhuijzen PS, Clarkson AN, Ahring PK, Chebib M: Zolpidem is a potent stoichiometry-selective modulator of α1β3 GABAA receptors: evidence of a novel benzodiazepine site in the α1-α1 interface . In: Sci Rep . 6, June 2016, p. 28674. doi : 10.1038 / srep28674 . PMID 27346730 . PMC 4921915 (free full text).
- ↑ a b c d Information for professionals for zolpidem tartrate. Status: September 2003 ( RTF ; 51 kB) sample text database of the Federal Institute for Drugs and Medical Devices (BfArM).
- ^ F. Hoffmann, M. Pfannkuche and G. Glaeske: “High consumption of zolpidem and zopiclone - cross-sectional study based on health insurance data.” Neurologist. 2008 Jan; 79 (1): 67-72 .
- ^ Rao RV, Sameer M. Zolpidem dependence . In: Indian J Pharmacol 2005; 37: 412-413.
- ↑ IA Liappas et al .: zolpidem dependence case series: possible neurobiological mechanisms and clinical management . In: Journal of Psychopharmacology , Vol. 17, No. 1: 131-135 (2003).
- ↑ FDA: FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR , warning notice , first edition 2013, update from January 15, 2016.
- ↑ ADR of zolpidem
