Tetrazepam
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| Non-proprietary name | Tetrazepam | |||||||||||||||
| other names |
7-chloro-5- (cyclohex-1-enyl) -1-methyl-1,3-dihydro-2 H -1,4-benzodiazepin-2-one ( IUPAC ) |
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| Molecular formula | C 16 H 17 ClN 2 O | |||||||||||||||
| Brief description |
yellow-brown crystals |
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| Molar mass | 288.77 g · mol -1 | |||||||||||||||
| Physical state |
firmly |
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| Melting point |
144 ° C |
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| solubility |
bad in water: 26.4 mg l −1 (at 25 ° C) |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||
Tetrazepam is a drug from the group of benzodiazepines with muscle-relaxing , anti-anxiety and sedating effects. Tetrazepam is indicated for pain reflective muscle tension, especially as a result of diseases of the spine and the joints near the axis and for spastic syndromes that can be traced back to a pathologically increased muscle tension. A second field of application are anxiety disorders and panic attacks .
pharmacology
application areas
Tetrazepam is used as a muscle relaxant for pain reflex muscle tension and spastic syndromes that are due to abnormally increased muscle tension, as well as for neurogenic contractures and muscle hypertension.
Pharmacokinetics
The bioavailability is 90–100%, maximum plasma concentrations are reached after 1.5–2 hours, plasma protein binding approx. 70%, plasma half-life 12–18 hours, steady-state concentrations after approx. Three days, elimination occurs after hepatic metabolism in glucuronides predominantly renal, equivalent dose (= 10 mg diazepam) 50 mg.
Mechanism of action
The synaptic inhibition mediated by GABA is promoted (released GABA is more effective), increased Cl influx, reduction in the excitability of the neuron membrane, inhibition of the mono- and polysynaptic reflex arcs, dampening of muscle tone, additional tension, excitation, anxiety-dampening, sedating, hypnotic and anticonvulsant effects.
Side effects
Characteristic side effects of tetrazepam are fatigue, slow reactions, hallucinations and, less often, unsteady gait due to muscle weakness , as well as depressive moods. In the first few days of treatment, you should therefore avoid (actively) driving a car or working with dangerous machinery (reaction slowdown). Movement and articulation disorders , drowsiness , nausea and vomiting can also be observed (1–10%). There is also the possibility of the effect being reversed, i.e. acute states of excitement (fear, suicidality , sleep disorders, tantrums or muscle cramps) can occur.
Furthermore, anterograde amnesias can develop , which in principle can occur with all benzodiazepines .
Tetrazepam can cause severe skin reactions: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), erythema multiforme and DRESS syndrome ( drug rash with eosinophilia and systemic symptoms ) have been observed. Due to a decision by the European Commission, the approval of drugs containing tetrazepam is suspended until the risk-benefit ratio has been clarified (see legal status in Germany, approval in other countries ).
Dependency potential
The active ingredient tetrazepam can lead to addiction after just a short ingestion . When the therapy with tetrazepam is stopped, the dose should be reduced slowly, as otherwise severe withdrawal syndromes, both mentally and physically , can occur. If the drug is stopped suddenly, it can lead to increased dreaming after 2-4 days of insomnia. In addition, anxiety, states of tension or depression can reappear more intensely.
Interactions
The effects of other substances acting in the central nervous system , especially alcohol , can be increased if taken at the same time as tetrazepam.
Centrally acting drugs; Alcohol (mutual effect enhancement); Muscle relaxants (the effects of which are amplified); Cimetidine , omeprazole (tetrazepam effect is increased); Clozapine (risk of respiratory / circulatory failure)
Since Tetrazepam via the cytochrome P450 - enzyme system CYP 3A4 metabolized is, inhibitors of this enzyme system such. B. cimetidine or grapefruit products , the effect of tetrazepam increase.
Legal status in Germany, approval in other countries
In Germany, drugs containing tetrazepam may no longer be prescribed or dispensed since August 1, 2013. Until then, tetrazepam was a marketable and prescription narcotic drug in the Federal Republic of Germany due to its listing in Appendix 3 to the Narcotics Act (BtMG).
Introduced on the market in France in 1967, tetrazepam has only been introduced in a few European countries, including Germany and Austria, but not in Great Britain and the USA.
Within the framework of pharmacovigilance , severe skin reactions (see section on side effects ) have been observed in France after taking tetrazepam, some of which are fatal. The French medicines authority ANSM recommended a national marketing ban and initiated a European risk assessment procedure in December 2012 with the aim of a Europe-wide ban. On the recommendation of the Pharmacovigilance Risk Assessment Committee (PRAC ) located in the European Medicines Agency (EMA) , the European Commission decided in May 2013 that approvals for tetrazepam-containing drugs in the member states should be suspended until August 2015 and the risk-benefit assessment To clarify the relationship.
See also
Trade names
Musaril (D), Rilex (D), various generics (D, A)
literature
- Detlev Schneider, Frank Richling: Checklist Medicines AZ . 5th edition. Thieme, Stuttgart 2008, ISBN 978-3-13-130855-9 .
Individual evidence
- ↑ Entry on tetrazepam. In: Römpp Online . Georg Thieme Verlag, accessed on July 7, 2014.
- ↑ a b c Entry on tetrazepam in the ChemIDplus database of the United States National Library of Medicine (NLM)
- ↑ There is not yet a harmonized classification for this substance . A labeling of tetrazepam in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was accessed on July 12, 2020, is shown, which is derived from a self-classification by the distributor .
- ↑ Christian Madler, Karl Werdan, Johannes Siegrist: Akutmedizin- The first 24 hours: The NAW, page 783 . Elsevier, Urban & Fischer Verlag, Munich 2009, ISBN 978-3-437-22511-6 . Online: limited preview in Google Book search.
- ↑ Aktories et al .: General and Special Pharmacology and Toxicology 9th ed., Pp. 336, 337.
- ↑ Suspended approval: No tetrazepam from August 1, 2013 - notification from the Deutsche Apotheker Zeitung of June 24, 2013.
- ↑ Severe skin reactions with tetrazepam. Deutsches Ärzteblatt, January 15, 2013.
- ↑ Tetrazepam-containing medicines - Article-107i procedure - Rationale for triggering (PDF; 93 kB) from January 14, 2013, European Medicines Agency (EMA).
- ↑ Tetrazepam-containing medicines , procedure overview of the European Medicines Agency (EMA).
- ↑ C (2013) 3344 final - Implementing decision of the Commission of 29 May 2013 regarding the authorizations for human medicinal products with the active ingredient "Tetrazepam" according to Article 107i of Directive 2001/83 / EC of the European Parliament and of the Council (PDF; 50 kB) .
- ↑ Medicines containing tetrazepam (e.g. Musaril®): Order to suspend approvals in the context of the implementation of the decision of the Commission. BfArM , July 5, 2013, accessed May 8, 2017 .
