Lormetazepam
Clinical data | |
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Trade names | Noctamid, Loramet, others |
Other names | Methyllorazepam; Methyl-lorazepam; N-Methyllorazepam; Ro 5-5516 |
AHFS/Drugs.com | International Drug Names |
Pregnancy category |
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intravenous[1] | |
Drug class | Benzodiazepine |
ATC code | |
Legal status | |
Legal status |
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Pharmacokinetic data | |
Bioavailability | 80% |
Metabolism | Hepatic |
Elimination half-life | 10–12 hours |
Excretion | Renal |
Identifiers | |
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JSmol) | |
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Lormetazepam, sold under the brand name Noctamid among others, is a drug which is a short to intermediate acting 3-hydroxy[3] benzodiazepine derivative and temazepam analogue.[4] It possesses hypnotic, anxiolytic, anticonvulsant, sedative, and skeletal muscle relaxant properties.
It was patented in 1961 and came into medical use in 1980.[5] Lormetazepam is not approved for sale in the United States or Canada. It is licensed in the UK as 0.5 and 1 mg tablets for short-term treatment (2–4 weeks) of moderately severe insomnia. It is licensed in the Netherlands as 1 and 2 mg tablets, under the brand names Loramet and Noctamid and as generic, available from several manufacturers. It is sold in Poland as Noctofer. A Dutch analysis stated that lormetazepam could be suitable to be included in drug prescribing formularies, although zolpidem, zopiclone, and temazepam appear better.[6]
Medical uses
Lormetazepam is considered a hypnotic benzodiazepine and is officially indicated for moderate-to-severe insomnia. Lormetazepam is a short-acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep or falling asleep. Hypnotics should only be used on a short-term basis or, in those with chronic insomnia, on an occasional basis.[7]
Side effects
Side effects of lormetazepam are similar to those of other hypnotic benzodiazepines and can for the most part be regarded as a class effect.[
Although lormetazepam has been associated with adversely affecting immediate and delayed recall memory functions,[9] studies have shown that lormetazepam's amnesic properties may be lesser compared to other hypnotic benzodiazepines. For example, in a 1984 study comparing the amnesic effects of lormetazepam to temazepam and flurazepam showed that amnesia was smallest after lormetazepam and greatest after temazepam, which had produced greater amnesia than both lormetazepam and flurazepam by a significant margin.[10]
Side effects of lormetazepam include:
- Somnolence
- Paradoxical increase in aggression
- Lightheadedness
- Confusion
- Muscle weakness
- Ataxia (particularly in the elderly)
- Anterograde amnesia
- Headache
- Vertigo
- Hypotension
- Salivation changes
- Gastrointestinal disturbances
- Visual disturbances
- Dysarthria
- Tremor
- Changes in libido
- Urinary incontinence
- Urinary retention
- Blood disorders and jaundice
- Skin reactions
- Dependence and withdrawal reactions
Residual "hangover" effects after nighttime administration of lormetazepam such as sleepiness, impaired psychomotor and
Benzodiazepines require special precaution if used during pregnancy, in children, in alcohol- or drug-dependent individuals and individuals with
Tolerance, dependence, and withdrawal
The risks of tolerance, dependence, and withdrawal are very low when the drug is used for 2–4 weeks only, and lormetazepam is generally a safe and effective drug when used for no longer than 2–4 weeks. Some sleep disturbance in the form of rebound insomnia can, however, occur even after short-term usage of 7 days.[15] Those with a history of addiction may be at increased risk of problems of tolerance and dependence especially those with a past history of dependency on sedative hypnotic drugs.
Lormetazepam as with other benzodiazepines is generally only recommended for short-term use (2–4 weeks) due to tolerance and loss of efficacy. Tolerance to and loss of the sedative effects of benzodiazepine hypnotics can occur within 14 days of regular use.[16] Some studies however suggest such treatments retain their effectiveness in the long term[17][18][19] - such a lack of consistency in the findings of many studies could be due to the variation of responses to benzodiazepine treatment.
Dependence is the medical term for addiction. Dependence can either be psychological and/or physical. Psychological dependence can manifest itself as a reliance on a drug to cope with everyday life or in the form of craving. Physical dependence occurs due to physiological adaptations occurring as the body attempts to overcome the drugs effects which is known as tolerance and the continuing need to take the drug to avoid or suppress withdrawal symptoms which can sometimes resemble the original condition being treated. When the dose or the drug is discontinued withdrawal symptoms typically occur. Lormetazepam as with all other benzodiazepines produces both physical and psychological dependence but the main problem of concern is physical dependence which appears in the form of the benzodiazepine withdrawal syndrome after the dosage is reduced or the drug is stopped completely.[20] The dependence induced by lormetazepam is related to changes in the sensitivity of the GABA-BZD receptor complex.[21]
Withdrawal symptoms typically subside after 4–8 weeks but in approximately 10-15% of individuals symptoms can persist for many months[22] and in rare cases years.[23] Some "Withdrawal Symptoms" can emerge despite a constant dosage with the body needing extra dosage in order to feel normal. This is sometimes associated with dosage escalation.
Lormetazepam has a short to intermediate half-life of approximately 10–12 hours. Shorter acting benzodiazepine compounds are generally associated with a more intense and immediate withdrawal reaction compared to longer acting benzodiazepines. For this reason it is generally recommended to cross from lormetazepam to an equivalent dose of diazepam to gradually taper the dosage.[24]
Pharmacology
The bioavailability of lormetazepam was found to be 80%.[25]
Lormetazepam and other benzodiazepine drugs act as positive modulators at the GABAA benzodiazepine receptor complex. Lormetazepam binds to the benzodiazepine receptor which in turn enhances the effect of the GABAA receptor producing its therapeutic effects as well as adverse effects. When lormetazepam binds to the benzodiazepine receptor sites in sufficient quantities it produces sedation which is used clinically as a therapeutic treatment for insomnia. Lormetazepam alters the brain electrical activity which has been studied via EEG readings.[26] Lormetazepam appears to be more selective in the type of benzodiazepine receptor it binds to showing a higher affinity for the omega 1 receptor which is responsible for sedation.[27] Changes in EEG can therefore be used to measure the sedative sleep promoting properties of lormetazepam.
Chemistry
Stereochemistry
Lormetazepam has a
Enantiomers of lormetazepam | |
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(R)-lormetazepam CAS number: 113679-56-4 |
(S)-lormetazepam CAS number: 113679-54-2 |
Industry
Brand names
Trade names include Aldosomnil, Dilamet, Ergocalm, Loramet, Loretam, Metatop, Minias, Noctamid, Noctamide, Noctofer, Nocton, Pronoctan, Sedaben, Sedalam, and Stilaze.
References
- PMID 32468272.
- ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
- PMID 1685875.
- ^ PMID 6120717.
- ISBN 9783527607495.
- PMID 10163418.
- S2CID 46560074.
- S2CID 23167620.
- S2CID 1680477.
- PMID 6147838.
- S2CID 25592318.
- PMID 19900604.
- S2CID 13440208.
- S2CID 26351598.
- S2CID 694106.
- ^ Smith AE (1989). "Benzodiazepines - Use & Abuse - A Guide for Prescribers". New Zealand Department of Health.
- PMID 6121605.
- S2CID 44857913.
- PMID 17702264.
- doi:10.3928/0048-5713-19950301-09. Archived from the originalon 21 August 2006.
- PMID 8803645.
- ^ Ashton CH. "Benzodiazepines: How They Work And How To Withdraw".
- S2CID 23530701. Archived from the originalon 11 June 2007.
- ^ "Benzodiazepines and Your Patients: A Management Programme". Roche Products (UK) Ltd. 1990.
- S2CID 19327058.
- PMID 6124982.
- PMID 1687574.
- ISBN 978-3-946057-10-9, S. 196.
External links
- "Lormetazepam". Inchem.org.