Bromazepam Explained

Watchedfields:changed
Verifiedrevid:413835339
Iupac Name:7-bromo-5-(pyridin-2-yl)-1H-benzo[''e''][1,4]diazepin-2(3H)-one
Width:222
Tradename:Lexotan, Lexotanil, others
Legal Br:B1
Legal Br Comment:[1]
Legal Ca:Schedule IV
Legal De:Rx-only/Anlage III
Legal Uk:Class C
Legal Us:Schedule IV
Addiction Liability:High[2]
Routes Of Administration:By mouth
Bioavailability:84%
Protein Bound:70%
Metabolism:Liver

P450

Metabolites:3-hydroxybromazepam
Elimination Half-Life:12–20 hours (avg. 17hr)[3]
Excretion:Urine 69%, as metabolites
Cas Number:1812-30-2
Atc Prefix:N05
Atc Suffix:BA08
Pubchem:2441
Drugbank:DB01558
Chemspiderid:2347
Unii:X015L14V0O
Kegg:D01245
Chebi:31302
Chembl:277062
C:14
H:10
Br:1
N:3
O:1
Smiles:C1C(=O)NC2=C(C=C(C=C2)Br)C(=N1)C3=CC=CC=N3
Stdinchi:1S/C14H10BrN3O/c15-9-4-5-11-10(7-9)14(17-8-13(19)18-11)12-3-1-2-6-16-12/h1-7H,8H2,(H,18,19)
Stdinchikey:VMIYHDSEFNYJSL-UHFFFAOYSA-N

Bromazepam, sold under many brand names, is a benzodiazepine. It is mainly an anti-anxiety agent with similar side effects to diazepam. In addition to being used to treat anxiety or panic states, bromazepam may be used as a premedicant prior to minor surgery. Bromazepam typically comes in doses of 3 mg and 6 mg tablets.[4]

It was patented in 1961 by Roche and approved for medical use in 1974.[5]

Medical uses

Medical uses include treatment of severe anxiety.[6] Despite certain side effects and the emergence of alternative products (e.g. pregabalin), benzodiazepine medication remains an effective way of reducing problematic symptoms, and is typically deemed effective by patients[7] [8] and medical professionals.[9] [10] [11] Similarly to other intermediate-acting depressants, it may be used as hypnotic medication[12] or in order to mitigate withdrawal effects of alcohol consumption.[13] [14] [15]

Pharmacology

Bromazepam is a "classical" benzodiazepine; other classical benzodiazepines include: diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, flurazepam, and clorazepate.[16] Its molecular structure is composed of a diazepine connected to a benzene ring and a pyridine ring, the benzene ring having a single nitrogen atom that replaces one of the carbon atoms in the ring structure.[17] It is a 1,4-benzodiazepine, which means that the nitrogens on the seven-sided diazepine ring are in the 1 and 4 positions.

Bromazepam binds to the GABA receptor GABAA, causing a conformational change and increasing the inhibitory effects of GABA. It acts as a positive modulator, increasing the receptors' response when activated by GABA itself or an agonist (such as alcohol). As opposed to barbital, BZDs are not GABA-receptor activators and rely on increasing the neurotransmitter's natural activity.[18] Bromazepam is an intermediate-acting benzodiazepine, is moderately lipophilic compared to other substances of its class[19] and metabolised hepatically via oxidative pathways.[20] It does not possess any antidepressant or antipsychotic qualities.[21]

After night time administration of bromazepam a highly significant reduction of gastric acid secretion occurs during sleep followed by a highly significant rebound in gastric acid production the following day.[22]

Bromazepam alters the electrical status of the brain causing an increase in beta activity and a decrease in alpha activity in EEG recordings.[23]

Pharmacokinetics

Bromazepam is reported to be metabolized by a hepatic enzyme belonging to the Cytochrome P450 family of enzymes. In 2003, a team led by Oda Manami at Oita Medical University reported that CYP3A4, a member of the Cytochrome P450 family, was not the responsible enzyme since itraconazole, a known inhibitor of CYP3A4, did not affect its metabolism.[24] In 1995, J. van Harten at the Solvay Pharmaceutical Department of Clinical Pharmacology in Weesp reported that fluvoxamine, which is a potent inhibitor of CYP1A2, a less potent CYP3A4 inhibitor, and a negligible inhibitor of CYP2D6, does inhibit its metabolism.

The major metabolite of bromazepam is hydroxybromazepam,[24] which is an active agent too and has a half-life approximately equal to that of bromazepam.

Side-effects

Bromazepam is similar in side effects to other benzodiazepines. The most common side effects reported are drowsiness, sedation, ataxia, memory impairment, and dizziness.[25] Impairments to memory functions are common with bromazepam and include a reduced working memory and reduced ability to process environmental information.[26] [27] [28] A 1975 experiment on healthy, male college students exploring the effects of four different drugs on learning capacity observed that taking bromazepam alone at 6 mg 3 times daily for 2 weeks impaired learning capacities significantly. In combination with alcohol, impairments in learning capacity became even more pronounced.[29] Various studies report impaired memory, visual information processing and sensory data and impaired psychomotor performance;[30] [31] [32] deterioration of cognition including attention capacity and impaired co-ordinative skills;[33] [34] impaired reactive and attention performance, which can impair driving skills;[35] drowsiness and decrease in libido.[36] [37] Unsteadiness after taking bromazepam is, however, less pronounced than other benzodiazepines such as lorazepam.[38]

On occasion, benzodiazepines can induce extreme alterations in memory such as anterograde amnesia and amnesic automatism, which may have medico-legal consequences. Such reactions occur usually only at the higher dose end of the prescribing spectrum.[39]

Very rarely, dystonia can develop.[40]

Up to 30% treated on a long-term basis develop a form of dependence, i.e. these patients cannot stop the medication without experiencing physical and/or psychological benzodiazepine withdrawal symptoms.

Leukopenia and liver-damage of the cholestatic type with or without jaundice (icterus) have additionally been seen; the original manufacturer Roche recommends regular laboratory examinations to be performed routinely.

Ambulatory patients should be warned that bromazepam may impair the ability to drive vehicles and to operate machinery. The impairment is worsened by consumption of alcohol, because both act as central nervous system depressants. During the course of therapy, tolerance to the sedative effect usually develops.

Frequency and seriousness of adverse effects

As with all medication, the frequency and seriousness of side-effects varies greatly depending on quantities consumed.[41] [42] In a study about bromazepam's negative effects on psychomotor skills and driving ability, it was noted that 3 mg doses caused minimal impairment.[43] It also appeared that impairment may be tied to methods of testing more so than on the product's intrinsic activity.[44]

Moreover, side-effects other than drowsiness, dizziness and ataxia seem to be rare[45] and not experienced by more than a few percent of users. The use of other, comparable medication seems to display an identically moderate side-effect profile.[46] [47] [48]

Tolerance, dependence and withdrawal

Prolonged use of bromazepam can cause tolerance and may lead to both physical and psychological dependence on the drug, and as a result, it is a medication which is controlled by international law. It is nonetheless important to note that dependence, long-term use and misuse occur in a minority of cases[49] [50] [51] and are not representative of most patients' experience with this type of medication.[52] [53]

It shares with other benzodiazepines the risk of abuse, misuse, psychological dependence or physical dependence.[54] [55] A withdrawal study demonstrated both psychological dependence and physical dependence on bromazepam including marked rebound anxiety after 4 weeks chronic use. Those whose dose was gradually reduced experienced no withdrawal.[56]

Patients treated with bromazepam for generalised anxiety disorder were found to experience withdrawal symptoms such as a worsening of anxiety, as well as the development of physical withdrawal symptoms when abruptly withdrawn bromazepam.[57] Abrupt or over rapid withdrawal from bromazepam after chronic use even at therapeutic prescribed doses can lead to a severe withdrawal syndrome including status epilepticus and a condition resembling delerium tremens.[58] [59] [60]

Animal studies have shown that chronic administration of diazepam (or bromazepam) causes a decrease in spontaneous locomotor activity, decreased turnover of noradrenaline and dopamine and serotonin, increased activity of tyrosine hydroxylase and increased levels of the catecholamines. During withdrawal of bromazepam or diazepam a fall in tryptophan, serotonin levels occurs as part of the benzodiazepine withdrawal syndrome.[61] Changes in the levels of these chemicals in the brain can cause headaches, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, dysphoria, dizziness, derealization, depersonalization, numbness/tingling of extremities, hypersensitivity to light, sound, and smell, perceptual distortions, nausea, vomiting, diarrhea, appetite loss, hallucinations, delirium, seizures, tremor, stomach cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, short-term memory loss, and hyperthermia.[62] [63]

Overdose

See main article: article and Benzodiazepine overdose. Bromazepam is commonly involved in drug overdoses.[64] A severe bromazepam benzodiazepine overdose may result in an alpha pattern coma type.[65] The toxicity of bromazepam in overdosage increases when combined with other CNS depressant drugs such as alcohol or sedative hypnotic drugs.[66] Similarly to other benzodiazepines however, being a positive modulator of certain neuroreceptors and not an agonist, the product has reduced overdose potential compared to older products of the barbiturate class. Its consumption alone is very seldom fatal in healthy adults.[67] [68]

Bromazepam was in 2005 the most common benzodiazepine involved in intentional overdoses in France.[69] Bromazepam has also been responsible for accidental poisonings in companion animals. A review of benzodiazepine poisonings in cats and dogs from 1991 to 1994 found bromazepam to be responsible for significantly more poisonings than any other benzodiazepine.[70]

Contraindications

Benzodiazepines require special precaution if used in elderly, pregnant, child, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.[71]

Special populations

Interactions

Cimetidine, fluvoxamine and propranolol causes a marked increase in the elimination half-life of bromazepam leading to increased accumulation of bromazepam.[72] [76] [77]

Society and culture

Drug misuse

See also: Benzodiazepine use disorder. Bromazepam has a similar misuse risk as other benzodiazepines such as diazepam.[78] In France car accidents involving psychotropic drugs in combination with alcohol (itself a major contributor) found benzodiazepines, mainly diazepam, nordiazepam, and bromazepam, to be the most common drug present in the blood stream, almost twice that of the next-most-common drug cannabis.[79] Bromazepam has also been used in serious criminal offences including robbery, homicide, and sexual assault.[80] [81] [82]

Brand names

It is marketed under several brand names, including, Brozam, Lectopam, Lexomil, Lexotan, Lexilium, Lexaurin, Brazepam, Rekotnil, Bromaze, Somalium, Lexatin, Calmepam, Zepam and Lexotanil.[83]

Legal status

Bromazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[84]

Synthesis

See also

External links

Notes and References

  1. Web site: Anvisa . Brazilian Health Regulatory Agency . 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. live . https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 . 2023-08-03 . 2023-08-16 . . pt-BR . 2023-04-04.
  2. Web site: Bromazepam: Uses, Interactions, Mechanism of Action . 2024-02-25. DrugBank Online.
  3. Web site: Lexotan (bromazepam) Product Insert . Roche . 23 October 2012 .
  4. Web site: Bromazepam. Pharmaceutical Benefits Scheme (PBS). Australian Government - Department of Health. 23 March 2014.
  5. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 53X . en.
  6. Web site: Content Not Available. www.uptodate.com. 2017-09-07.
  7. Podiwinsky F, Jellinger K . [Bromazepam in the treatment of somatized psychogenic disorders (author's transl)] . German . Wiener Klinische Wochenschrift . 91 . 7 . 240–244 . March 1979 . 34934 . Bromazepam in the treatment of somatized psychogenic disorders .
  8. Laxenaire M, Kahn JP, Marchand P . [A clinical trial of bromazepam (author's transl)] . French . La Nouvelle Presse Médicale . 11 . 22 . 1699–1701 . May 1982 . 6124936 . A clinical trial of bromazepam .
  9. Ropert R, Bernes J, Dachary JM . [Efficacy and tolerance of alprazolam and bromazepam in flexible doses. Double-blind study in 119 ambulatory anxious patients] . French . L'Encéphale . 13 . 2 . 89–95 . 1987 . 2885173 . Efficacy and tolerance of alprazolam and bromazepam in flexible doses. Double-blind study in 119 ambulatory anxious patients .
  10. Hallett C, Dean BC . Bromazepam: acute benefit-risk assessment in general practice . Current Medical Research and Opinion . 8 . 10 . 683–688 . 11 August 2008 . 6144455 . 10.1185/03007998409110117 .
  11. Web site: Bromazépam . 7 September 2016 . Haute Autorité de santé (HAS) . French .
  12. Web site: Bromazepam.
  13. Web site: Bromazépam . Répertoire des Spécialités Pharmaceutiques . ANSM: Agence Nationale de Sécurité du Médicament et des Produits de Santé (French: National Security Agency of Medicines and Health Products) .
  14. Chweh AY, Lin YB, Swinyard EA . Hypnotic action of benzodiazepines: a possible mechanism . Life Sciences . 34 . 18 . 1763–1768 . April 1984 . 6145073 . 10.1016/0024-3205(84)90576-9 .
  15. Cordingley GJ, Dean BC, Hallett C . A multi-centre, double-blind parallel trial of bromazepam ('Lexotan') and lorazepam to compare the acute benefit-risk ratio in the treatment of patients with anxiety . Current Medical Research and Opinion . 9 . 7 . 505–510 . 11 August 2008 . 2863089 . 10.1185/03007998509109625 .
  16. Braestrup C, Squires RF . Pharmacological characterization of benzodiazepine receptors in the brain . European Journal of Pharmacology . 48 . 3 . 263–270 . April 1978 . 639854 . 10.1016/0014-2999(78)90085-7 .
  17. http://www.eutimia.com/psicofarmacos/ansioliticos/bromazepam.htm Bromazepam
  18. Poisbeau P, Gazzo G, Calvel L . Anxiolytics targeting GABAA receptors: Insights on etifoxine . The World Journal of Biological Psychiatry . 19 . sup1 . S36–S45 . 11 September 2018 . 30204559 . 10.1080/15622975.2018.1468030 . free .
  19. Adeyemo MA, Idowu SO . Correlation of lipophilicity descriptors with pharmacokinetic parameters of selected benzodiazepines . African Journal of Biomedical Research . 25 November 2016 . 19 . 3 . 213–218 .
  20. Oelschläger H . [Chemical and pharmacologic aspects of benzodiazepines] . German . Schweizerische Rundschau für Medizin Praxis . 78 . 27–28 . 766–772 . July 1989 . 2570451 .
  21. Amphoux G, Agussol P, Girard J . [The action of bromazepam on anxiety (author's transl)] . French . La Nouvelle Presse Médicale . 11 . 22 . 1738–1740 . May 1982 . 6124947 . The action of bromazepam on anxiety .
  22. Stacher G, Stärker D . Inhibitory effect of bromazepam on basal and betazole-stimulated gastric acid secretion in man . Gut . 15 . 2 . 116–120 . February 1974 . 4820635 . 1412901 . 10.1136/gut.15.2.116 .
  23. Fink M, Weinfeld RE, Schwartz MA, Conney AH . Blood levels and electroencephalographic effects of diazepam and bromazepam . Clinical Pharmacology and Therapeutics . 20 . 2 . 184–191 . August 1976 . 7375 . 10.1002/cpt1976202184 . 38155674 .
  24. Oda M, Kotegawa T, Tsutsumi K, Ohtani Y, Kuwatani K, Nakano S . The effect of itraconazole on the pharmacokinetics and pharmacodynamics of bromazepam in healthy volunteers . European Journal of Clinical Pharmacology . 59 . 8–9 . 615–619 . November 2003 . 14517708 . 10.1007/s00228-003-0681-4 . 24131632 .
  25. Web site: LECTOPAM®. RxMed. 23 March 2014.
  26. Münte TF, Gehde E, Johannes S, Seewald M, Heinze HJ . Effects of alprazolam and bromazepam on visual search and verbal recognition memory in humans: a study with event-related brain potentials . Neuropsychobiology . 34 . 1 . 49–56 . 1996 . 8884760 . 10.1159/000119291 .
  27. Montenegro M, Veiga H, Deslandes A, Cagy M, McDowell K, Pompeu F, Piedade R, Ribeiro P . 6 . [Neuromodulatory effects of caffeine and bromazepam on visual event-related potential (P300): a comparative study] . Arquivos de Neuro-Psiquiatria . 63 . 2B . 410–415 . June 2005 . 16059590 . 10.1590/s0004-282x2005000300009 . free .
  28. Cunha M, Portela C, Bastos VH, Machado D, Machado S, Velasques B, Budde H, Cagy M, Basile L, Piedade R, Ribeiro P . 6 . Responsiveness of sensorimotor cortex during pharmacological intervention with bromazepam . Neuroscience Letters . 448 . 1 . 33–36 . December 2008 . 18938214 . 10.1016/j.neulet.2008.10.024 . 22491979 .
  29. Liljequist R, Linnoila M, Mattila MJ, Saario I, Seppälä T . Effect of two weeks' treatment with thioridazine, chlorpromazine, sulpiride and bromazepam, alone or in combination with alcohol, on learning and memory in man . Psychopharmacologia . 44 . 2 . 205–208 . October 1975 . 710 . 10.1007/BF00421011 . 36415883 .
  30. Stacher G, Bauer P, Brunner H, Grünberger J . Gastric acid secretion, serum-gastrin levels and psychomotor function under the influence of placebo, insulin-hypoglycemia, and/or bromazepam . International Journal of Clinical Pharmacology and Biopharmacy . 13 . 1 . 1–10 . January 1976 . 2560 .
  31. Bourin M, Auget JL, Colombel MC, Larousse C . Effects of single oral doses of bromazepam, buspirone and clobazam on performance tasks and memory . Neuropsychobiology . 22 . 3 . 141–145 . 1989 . 2577220 . 10.1159/000118609 .
  32. Puga F, Sampaio I, Veiga H, Ferreira C, Cagy M, Piedade R, Ribeiro P . The effects of bromazepam on the early stage of visual information processing (P100) . Arquivos de Neuro-Psiquiatria . 65 . 4A . 955–959 . December 2007 . 18094853 . 10.1590/s0004-282x2007000600006 . free .
  33. Saario I . Psychomotor skills during subacute treatment with thioridazine and bromazepam, and their combined effects with alcohol . Annals of Clinical Research . 8 . 2 . 117–123 . April 1976 . 7178 .
  34. Jansen AA, Verbaten MN, Slangen JL . Acute effects of bromazepam on signal detection performance, digit symbol substitution test and smooth pursuit eye movements . Neuropsychobiology . 20 . 2 . 91–95 . 1988 . 2908134 . 10.1159/000118481 .
  35. Book: 10.1159/000399456 . Two Weeks' Treatment with Chlorpromazine, Thioridazine, Sulpiride, or Bromazepam: Actions and Interactions with Alcohol on Psychomotor Skills Related to Driving . Alcohol, Drugs and Driving . Modern Trends in Pharmacopsychiatry . 1976 . Seppälä T, Saario I, Mattila MJ . 11 . 85–90 . 9581 . 978-3-8055-2349-3 .
  36. Horseau C, Brion S . [Clinical trial of bromazepam. Thirty-four cases (author's transl)] . French . La Nouvelle Presse Médicale . 11 . 22 . 1741–1743 . May 1982 . 6124948 .
  37. Perret J, Zagala A, Gaio JM, Hommel M, Meaulle F, Pellat J, Pollak P . [Bromazepam in anxiety. Clinical evaluation (author's transl)] . French . La Nouvelle Presse Médicale . 11 . 22 . 1722–1724 . May 1982 . 6124942 .
  38. Patat A, Foulhoux P . Effect on postural sway of various benzodiazepine tranquillizers . British Journal of Clinical Pharmacology . 20 . 1 . 9–16 . July 1985 . 2862898 . 1400619 . 10.1111/j.1365-2125.1985.tb02792.x .
  39. Rager P, Bénézech M . [Memory gaps and hypercomplex automatisms after a single oral dose of benzodiazepines: clinical and medico-legal aspects] . French . Annales Médico-Psychologiques . 144 . 1 . 102–109 . January 1986 . 2876672 . Memory gaps and hypercomplex automatisms after a single oral dose of benzodiazepines: clinical and medico-legal aspects .
  40. Pérez Trullen JM, Modrego Pardo PJ, Vázquez André M, López Lozano JJ . Bromazepam-induced dystonia . Biomedicine & Pharmacotherapy . 46 . 8 . 375–376 . January 1992 . 1292648 . 10.1016/0753-3322(92)90306-r .
  41. Web site: LEXOMIL - Bromazépam - Posologie, Effets secondaires, Grossesse.
  42. Web site: How to Manage Common Drug Side Effects.
  43. Hobi V, Dubach UC, Skreta M, Forgo I, Riggenbach H . The subacute effect of bromazepam on psychomotor activity and subjective mood . The Journal of International Medical Research . 10 . 3 . 140–146 . 25 June 2016 . 6124470 . 10.1177/030006058201000302 . 25165191 .
  44. Hobi V, Dubach UC, Skreta M, Forgo J, Riggenbach H . The effect of bromazepam on psychomotor activity and subjective mood . The Journal of International Medical Research . 9 . 2 . 89–97 . 25 June 2016 . 6112173 . 10.1177/030006058100900201 . 21899896 .
  45. Web site: Side effect information for Bromazepam.
  46. Web site: Side effect information for Lorazepam.
  47. Web site: Side effect information for Diazepam.
  48. Web site: Notice patient - LORAZEPAM MYLAN 1 mg, comprimé pelliculé sécable - Base de données publique des médicaments.
  49. Yen CF, Ko CH, Chang YP, Yu CY, Huang MF, Yeh YC, Lin JJ, Chen CS . 6 . Dependence, misuse, and beliefs regarding use of hypnotics by elderly psychiatric patients taking zolpidem, estazolam, or flunitrazepam . Asia-Pacific Psychiatry . 7 . 3 . 298–305 . September 2015 . 25296384 . 10.1111/appy.12147 . 5782780 .
  50. Schmidt LG, Grohmann R, Müller-Oerlinghausen B, Otto M, Rüther E, Wolf B . Prevalence of benzodiazepine abuse and dependence in psychiatric in-patients with different nosology. An assessment of hospital-based drug surveillance data . The British Journal of Psychiatry . 154 . 6 . 839–843 . June 1989 . 2574611 . 10.1192/bjp.154.6.839 . 10441280 .
  51. Airagnes G, Lemogne C, Renuy A, Goldberg M, Hoertel N, Roquelaure Y, Limosin F, Zins M . 6 . Prevalence of prescribed benzodiazepine long-term use in the French general population according to sociodemographic and clinical factors: findings from the CONSTANCES cohort . BMC Public Health . 19 . 1 . 566 . May 2019 . 31088561 . 6518636 . 10.1186/s12889-019-6933-8 . free .
  52. Soyka M . Treatment of Benzodiazepine Dependence . The New England Journal of Medicine . 376 . 24 . 2399–2400 . June 2017 . 28614686 . 10.1056/NEJMc1705239 .
  53. Web site: HealthDay News . Psychiatry Advisor . Haymarket . Prevalence of Benzodiazepine Use 12.6 Percent in the United States. 3 January 2019.
  54. Rastogi RB, Lapierre YD, Singhal RL . Some neurochemical correlates of "rebound" phenomenon observed during withdrawal after long-term exposure to 1, 4-benzodiazepines . Progress in Neuro-Psychopharmacology . 2 . 1 . 43–54 . 1978 . 31644 . 10.1016/0364-7722(78)90021-8 .
  55. Laux G . [A case of Lexotanil dependence. Case report on tranquilizer abuse] . Der Nervenarzt . 50 . 5 . 326–327 . May 1979 . 37451 .
  56. Fontaine R, Chouinard G, Annable L . Rebound anxiety in anxious patients after abrupt withdrawal of benzodiazepine treatment . The American Journal of Psychiatry . 141 . 7 . 848–852 . July 1984 . 6145363 . 10.1176/ajp.141.7.848 .
  57. Chouinard G, Labonte A, Fontaine R, Annable L . New concepts in benzodiazepine therapy: rebound anxiety and new indications for the more potent benzodiazepines . Progress in Neuro-Psychopharmacology & Biological Psychiatry . 7 . 4–6 . 669–673 . 1983 . 6141609 . 10.1016/0278-5846(83)90043-X . 32967696 .
  58. Böning J . [Bromazepam withdrawal delirium - a psychopharmacological contribution to clinical withdrawal syndromes (author's transl)] . Der Nervenarzt . 52 . 5 . 293–297 . May 1981 . 6113557 .
  59. Thomas P, Lebrun C, Chatel M . De novo absence status epilepticus as a benzodiazepine withdrawal syndrome . Epilepsia . 34 . 2 . 355–358 . March 1993 . 8384109 . 10.1111/j.1528-1157.1993.tb02421.x . 45915803 .
  60. Fukuda M, Nakajima N, Tomita M . Generalized tonic-clonic seizures following withdrawal of therapeutic dose of bromazepam . Pharmacopsychiatry . 32 . 1 . 42–43 . January 1999 . 10071183 . 10.1055/s-2007-979188 . 260238907 .
  61. Agarwal RA, Lapierre YD, Rastogi RB, Singhal RL . Alterations in brain 5-hydroxytryptamine metabolism during the 'withdrawal' phase after chronic treatment with diazepam and bromazepam . British Journal of Pharmacology . 60 . 1 . 3–9 . May 1977 . 18243 . 1667179 . 10.1111/j.1476-5381.1977.tb16740.x .
  62. Web site: Professor Heather Ashton . 2002 . Benzodiazepines: How They Work and How to Withdraw .
  63. O'Connor RD . Benzodiazepine dependence--a treatment perspective and an advocacy for control . NIDA Research Monograph . 131 . 266–269 . 1993 . 8105385 .
  64. Gandolfi E, Andrade M . [Drug-related toxic events in the state of São Paulo, Brazil] . Portuguese . Revista de Saude Publica . 40 . 6 . 1056–1064 . December 2006 . 17173163 . 10.1590/s0034-89102006000700014 . Drug-related toxic events in the state of São Paulo, Brazil . free .
  65. Pasinato E, Franciosi A, De Vanna M . ["Alpha pattern coma" after poisoning with flunitrazepam and bromazepam. Case description] . Minerva Psichiatrica . 24 . 2 . 69–74 . 1983 . 6140613 .
  66. Marrache F, Mégarbane B, Pirnay S, Rhaoui A, Thuong M . Difficulties in assessing brain death in a case of benzodiazepine poisoning with persistent cerebral blood flow . Human & Experimental Toxicology . 23 . 10 . 503–505 . October 2004 . 15553176 . 10.1191/0960327104ht478cr . 19380042 . free . 2004HETox..23..503M .
  67. Löscher W, Rogawski MA . How theories evolved concerning the mechanism of action of barbiturates . Epilepsia . 53 . Suppl 8 . 12–25 . December 2012 . 23205959 . 10.1111/epi.12025 . 4675696 . free .
  68. Koyama K, Shimazu Y, Kikuno T, Kaziwara H, Sekiguti H . [Pharmacokinetics of bromazepam in 57 patients with acute drug intoxication] . Japanese . Chudoku Kenkyu . 16 . 1 . 51–56 . January 2003 . 12712542 . Pharmacokinetics of bromazepam in 57 patients with acute drug intoxication .
  69. Staikowsky F, Theil F, Candella S . [Trends in the pharmaceutical profile of intentional drug overdoses seen in the emergency room] . French . Presse Médicale . 34 . 12 . 842–846 . July 2005 . 16097205 . 10.1016/s0755-4982(05)84060-6 . Trends in the pharmaceutical profile of intentional drug overdoses seen in the emergency room .
  70. Bertini S, Buronfosse F, Pineau X, Berny P, Lorgue G . Benzodiazepine poisoning in companion animals . Veterinary and Human Toxicology . 37 . 6 . 559–562 . December 1995 . 8588297 .
  71. Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, Vennat B, Llorca PM, Eschalier A . 6 . Benzodiazepine dependence: focus on withdrawal syndrome . Annales Pharmaceutiques Françaises . 67 . 6 . 408–413 . November 2009 . 19900604 . 10.1016/j.pharma.2009.07.001 .
  72. Ochs HR, Greenblatt DJ, Friedman H, Burstein ES, Locniskar A, Harmatz JS, Shader RI . Bromazepam pharmacokinetics: influence of age, gender, oral contraceptives, cimetidine, and propranolol . Clinical Pharmacology and Therapeutics . 41 . 5 . 562–570 . May 1987 . 2882883 . 10.1038/clpt.1987.72 . 1099919 .
  73. Hobi V, Kielholz P, Dubach UC . [The effect of bromazepam on fitness to drive (author's transl)] . German . Munchener Medizinische Wochenschrift . 123 . 42 . 1585–1588 . October 1981 . 6118830 . The effect of bromazepam on fitness to drive .
  74. Web site: NAME OF THE MEDICINE LEXOTAN . 16 December 2008 . Hoffman LaRoche Pharmaceuticals . Hoffman LaRoche . 3 April 2008 . PDF . roche-australia.com . Australia . https://web.archive.org/web/20080719012817/http://www.roche-australia.com/downloads/lexotan-pi.cfm?action=get . 19 July 2008.
  75. Martens PR . A sudden infant death like syndrome possibly induced by a benzodiazepine in breast-feeding . European Journal of Emergency Medicine . 1 . 2 . 86–87 . June 1994 . 9422145 . 10.1097/00063110-199406000-00008 .
  76. Perucca E, Gatti G, Spina E . Clinical pharmacokinetics of fluvoxamine . Clinical Pharmacokinetics . 27 . 3 . 175–190 . September 1994 . 7988100 . 10.2165/00003088-199427030-00002 . 22472247 .
  77. van Harten J . Overview of the pharmacokinetics of fluvoxamine . Clinical Pharmacokinetics . 29. Suppl 1 . 1–9 . 1995 . 8846617 . 10.2165/00003088-199500291-00003 . 71812133 .
  78. Woods JH . [{{Google books|pA8XPwwoEMwC|page=59|plainurl=yes}} Progress report on the stimulant-depressant abuse liability evaluation project ]. NIDA Research Monograph . 49 . 59–62 . March 1984 . 6148695 .
  79. Staub C, Lacalle H, Fryc O . [Presence of psychotropic drugs in the blood of drivers responsible for car accidents, and who consumed alcohol at the same time] . French . Sozial- und Präventivmedizin . 39 . 3 . 143–149 . May 1994 . 8048274 . 10.1007/BF01299658 . Presence of psychotropic drugs in the blood of drivers responsible for car accidents, and who consumed alcohol at the same time . 19379856 .
  80. Brinkmann B, Fechner G, Püschel K . Identification of mechanical asphyxiation in cases of attempted masking of the homicide . Forensic Science International . 26 . 4 . 235–245 . December 1984 . 6519613 . 10.1016/0379-0738(84)90028-8 .
  81. de Boisjolly JM, Rougé-Maillart C, Roy PM, Roussel B, Turcant A, Delhumeau A . [Chemical submission] . French . Presse Médicale . 32 . 26 . 1216–1218 . August 2003 . 14506459 . Chemical submission .
  82. Djezzar S, Questel F, Burin E, Dally S . Chemical submission: results of 4-year French inquiry . International Journal of Legal Medicine . 123 . 3 . 213–219 . May 2009 . 18925406 . 10.1007/s00414-008-0291-x . 23902799 . French Network of Centers for Evaluation and Information on Pharmacodependence .
  83. Web site: Benzodiazepine Names. 2008-10-31. non-benzodiazepines.org.uk. dead. https://web.archive.org/web/20081208054743/http://www.non-benzodiazepines.org.uk/benzodiazepine-names.html. 2008-12-08.
  84. http://www.incb.org/pdf/e/list/green.pdf List of psychotropic substances under international control

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