Nitrazepam
Nitrazepam is a long-acting benzodiazepine hypnotic first synthesized in the late 1950s by Hoffmann-La Roche and introduced medically in 1965 under the brand name Mogadon. It possesses potent sedative, anxiolytic, amnestic, anticonvulsant, and muscle relaxant properties.1 Nitrazepam is primarily prescribed for short-term treatment of severe insomnia and disabling anxiety, reducing sleep onset time and increasing sleep duration.1 It is also used in managing myoclonic seizures.12
Contents
Dosage & Duration
Dosage
Duration
Subjective Effects
The experience is dominated by hypnotic sedation, muscle relaxation, and a marked reduction in anxiety, with sleep onset shortened and sleep duration extended. Its long duration means effects persist well past the intended sleep period, producing a lingering "hungover" quality the following day that includes sleepiness, slowed psychomotor performance, and impaired decision-making. Memory impairment is a defining feature, and at higher doses balance, speech, and coordination degrade noticeably. Paradoxical reactions such as excitement, stimulation, hallucinations, and hyperactivity are reported infrequently.
Physical
Pronounced skeletal muscle relaxation and heavy somnolence dominate, accompanied by muscle weakness and reduced physical performance. Ataxia, unsteadiness, dizziness, and vertigo impair balance and walking, with slurred speech at higher doses.
Cognitive
The headspace is calm and anxiety-free but progressively dulled, with reduced alertness, numbed emotions, inattention, and unreliable recall. Confusion and disorientation are more likely with chronic use or in older users, and depressed mood is a reported effect.
Emotional
Impairment
Suppressions
Visual
Tactile
Multisensory
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
Nitrazepam is a benzodiazepine that acts as a full agonist at central benzodiazepine receptors, which are associated with inhibitory GABA-A receptors.1 This binding enhances GABA activity at GABA-A receptors, producing sedative, hypnotic, anxiolytic, anticonvulsant, amnestic, and skeletal muscle relaxant effects.1 The anticonvulsant properties may be partly or entirely attributable to binding to voltage-gated sodium channels rather than benzodiazepine receptors, with benzodiazepines slowing recovery of sodium channels from inactivation. Nitrazepam also binds to peripheral-type benzodiazepine receptors. The muscle relaxant effects are produced via inhibition of polysynaptic pathways in the spinal cord.3 At high doses, nitrazepam decreases histamine turnover as a result of its action at the benzodiazepine-GABA receptor complex, and it has demonstrated cortisol-suppressing properties in humans.4
Pharmacokinetics
Nitrazepam is lipophilic and largely bound to plasma proteins,5 with high cerebral uptake. Oral bioavailability ranges from 53 to 94 percent, and food intake does not influence absorption rate or bioavailability. Peak plasma concentrations are reached approximately 2 hours after oral administration, with a range of 0.5 to 5 hours. The drug is metabolized hepatically by oxidative pathways.5 As a nitrobenzodiazepine, nitrazepam is metabolically activated by CYP3A4, which can generate reactive metabolites including free radicals.6 The elimination half-life ranges from 15 to 48 hours, with a mean of approximately 26 hours.7 Half-life is age-dependent, averaging around 29 hours in young people and extending to approximately 40 hours in the elderly.8 Nitrazepam is eliminated extremely slowly from the cerebrospinal fluid, with a half-life of 68 hours in that compartment.9
Dangerous
Highest riskThese combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
Unsafe
AvoidThere is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Benzodiazepines, GABAergic depressants
Harm Potential
Addiction & Dependence
Psychological
HighRecreational use is common and the drug is classified as habit-forming. Dependence can develop in as little as four weeks of regular use, with prescriptions recommended to not exceed seven to ten consecutive days.14
Physical
HighPhysical dependence develops readily with continued use, producing a withdrawal syndrome similar to alcohol and barbiturate withdrawal.14 Common withdrawal symptoms include anxiety, insomnia, concentration problems, and fatigue.14 Neonatal withdrawal syndrome can occur in infants born to mothers using nitrazepam during pregnancy.14
Toxicity
Severe liver toxicity has been reported; nitrobenzodiazepines including nitrazepam are more hepatotoxic than other benzodiazepines due to metabolic activation by CYP3A4.15
Long-term use may lead to development of cognitive deficits; elderly patients are particularly susceptible and may develop a disability characterized by general mental deterioration, inability to walk, incontinence, dysarthria, confusion, and disorientation from doses as low as 5 mg.
Can cause severe respiratory distress in children, including swallowing incoordination, bronchospasm, delayed cricopharyngeal relaxation, and respiratory depression potentially requiring ventilatory support; may promote parasympathetic overactivity leading to potentially fatal respiratory distress.16
Benzodiazepine use is associated with an increased risk of developing cancer.18
Psychosis Risk
Very infrequently, paradoxical reactions may occur including excitement, stimulation, hallucinations, hyperactivity, and insomnia.14
History & Culture
Nitrazepam was first synthesized in the late 1950s by a team of researchers at Hoffmann-La Roche in Switzerland. The compound was patented in 1961 and subsequently entered medical use in 1965, marketed under the brand name Mogadon among others.…
References
Source Pages
Citations
- (2021). MOGADON (Nitrazepam) Tablets BP 5 mg, 10 mg — Product Monograph. AA Pharma Inc.. https://www.aapharma.ca/downloads/en/PIL/2021/Mogadon_PM_EN.pdf12345
- Apotex Inc.. (2021). APO-NITRAZEPAM (Nitrazepam Tablets BP 5 mg and 10 mg) — Product Monograph. Health Canada / Apotex Inc.. https://pdf.hres.ca/dpd_pm/00065199.PDF1
- (November 1984). Investigation of the muscle relaxant activity of nitrazepam. Archives Internationales de Pharmacodynamie et de Thérapie, 272(1), 129–139. https://pubmed.ncbi.nlm.nih.gov/6517646/1
- (1992). Benzodiazepine-induced sedation and cortisol suppression. A placebo-controlled comparison of oxazepam and nitrazepam in healthy male volunteers. https://pubmed.ncbi.nlm.nih.gov/1349754/1
- (2010). APO-NITRAZEPAM Nitrazepam Tablets BP — Product Monograph. Apotex Inc.. https://www.e-lactancia.org/media/papers/Nitrazepam-DS-Apotex2010.pdf12
- Konishi K, Fukami T, Gotoh S, & Nakajima M. (2017). Identification of enzymes responsible for nitrazepam metabolism and toxicity in human. https://pubmed.ncbi.nlm.nih.gov/28606603/1
- Jochemsen R, Van Beusekom BR, Spoelstra P, & Breimer DD. (1983). Effect of age and liver cirrhosis on the pharmacokinetics of nitrazepam. 15(3), 295-302. https://pmc.ncbi.nlm.nih.gov/articles/PMC1427771/12
- Kangas L, Kanto J, & Leppanen A. (1979). Human pharmacokinetics of nitrazepam: effect of age and diseases. https://pubmed.ncbi.nlm.nih.gov/456400/12
- Kangas L, Kanto J, Siirtola T, & Pakkanen A. (1977). Cerebrospinal-fluid concentrations of nitrazepam in man. https://pubmed.ncbi.nlm.nih.gov/578380/12
- (1978). Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients. 57(1), 27–35. https://doi.org/10.1111/j.1600-0447.1978.tb06871.x12
- (1983). Hypnotic accumulation and hangover in elderly inpatients: a controlled double-blind study of temazepam and nitrazepam. 286(6359), 100–102. https://pmc.ncbi.nlm.nih.gov/articles/PMC1546430/1
- (December 1998). Benzodiazepines in the treatment of epilepsy in people with intellectual disability. Journal of Intellectual Disability Research, 42 Suppl 1(1), 80–92. https://pubmed.ncbi.nlm.nih.gov/10030438/1
- (1993). The role of nitrazepam in intractable seizures in childhood. 6(3), 189–194. https://doi.org/10.1016/s0896-6974(05)80089-11
- (2019). MOGADON (Nitrazepam Tablets BP 5 mg, 10 mg) Product Monograph — AA Pharma Inc.. AA Pharma Inc.. https://pdf.hres.ca/dpd_pm/00052939.PDF12345
- (February 2009). Metabolic activation of benzodiazepines by CYP3A4. Drug Metabolism and Disposition, 37(2), 345–351. https://doi.org/10.1124/dmd.108.0245211
- (September 1992). Nitrazepam-induced cricopharyngeal dysphagia, abnormal esophageal peristalsis and associated bronchospasm: probable cause of nitrazepam-related sudden death. Brain & Development, 14(5), 309–314. https://doi.org/10.1016/s0387-7604(12)80149-51
- (April 1999). Incidence of death in patients with intractable epilepsy during nitrazepam treatment. Epilepsia, 40(4), 492–496. https://doi.org/10.1111/j.1528-1157.1999.tb00746.x1
- (2017). Benzodiazepine drug use and cancer risk: a dose-response meta analysis of prospective cohort studies. https://doi.org/10.18632/oncotarget.220571
- Apotex Inc.. (2019-07-04). APO-NITRAZEPAM Product Monograph — Nitrazepam Tablets BP 5 mg and 10 mg. Apotex Inc.. https://pdf.hres.ca/dpd_pm/00052028.PDF1
- (October 2020). Optical Control of GABAA Receptors with a Fulgimide-Based Potentiator. Chemistry: A European Journal, 26(56), 12722–12727. https://doi.org/10.1002/chem.2020007101
- (n.d.). Controlled Drugs and Substances Act (SC 1996, c. 19) — Schedule IV, Item 18(24): Nitrazepam. https://laws-lois.justice.gc.ca/eng/acts/c-38.8/page-12.html1
- (n.d.). Health Canada Drug Product Database — MOGADON (DIN 00511536), AA Pharma Inc. https://produits-sante.canada.ca/dpd-bdpp/info?lang=eng&code=39921
- (n.d.). Health Canada Drug Product Database — Nitrazepam 5 mg products search (APO-NITRAZEPAM, SANDOZ NITRAZEPAM). https://health-products.canada.ca/dpd-bdpp/search-fast-recherche-rapide?lang=eng&no=01143450011
Further Reading
Automated synthesisInformation aggregated and synthesized using an autonomous workflow built by Josie Kins.
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