Bromazepam 1

Bromazepam

Bromazepam

Systematic (IUPAC) name

7-bromo-5-(pyridin-2-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one

Clinical data

Trade names Lexotan, Lexotanil

AHFS/Drugs.com Micromedex Detailed Consumer Information [1]

Pregnancy cat. D (USA)

Legal status Schedule IV(US)

Routes Oral

Pharmacokinetic data

Bioavailability 84%

Metabolism Hepatic

Half-life 12-20 hours

Bromazepam 2

Excretion Renal

Identifiers

CAS number 1812-30-2 [2] 

ATC code N05BA08 [3]

PubChem CID 2441 [4]

DrugBank DB01558 [5]

ChemSpider 2347 [6] 

UNII X015L14V0O [7] 

KEGG D01245 [8] 

ChEMBL CHEMBL277062 [9] 

Chemical data

Formula C14H10BrN3O

Mol. mass 316.2

 (what is this?)   (verify) [10]

Bromazepam (marketed under several brand names, including Lectopam, Lexotan, Lexilium, Lexaurin,Brazepam, Rekotnil, Bromaze, Somalium and Lexotanil) is a benzodiazepine derivative drug, patented by Rochein 1963 and developed clinically in the 1970s. It has mainly an anti-anxiety agent with similar side effects todiazepam (Valium). In addition to being used to treat anxiety or panic states, bromazepam may be used as apremedicant prior to minor surgery. Bromazepam typically comes in doses of 3 mg and 6 mg tablets. Bromazepam iscontraindicated and should be used with caution in women who are pregnant, the elderly, patients with a history ofalcohol or other substance abuse disorders and children. Prolonged use of bromazepam causes tolerance and maylead to both physical and psychological dependence on the drug, and as a result, it is a medication which iscontrolled by international law.

Indications• Short-term treatment of anxiety or panic attacks, if a benzodiazepine is required.• Premedication to alleviate anxiety before surgery.

Side-effectsBromazepam causes similar side effects to other benzodiazepines. The most common side effects reported aredrowsiness, sedation, ataxia, memory impairment, and dizziness. Impairments to memory functions are commonwith bromazepam and include a reduced working memory and reduced ability to process environmental information.A 1975 experiment on healthy, male college students exploring the effects of four different drugs on learningcapacity observed that taking Bromazepam alone at 6 mg 3 times daily for 2 weeks impaired learning capacitiessignificantly. In combination with alcohol impairments in learning capacity became even more pronounced.Impaired memory, visual information processing and sensory data and impaired psychomotor performance.Deterioration of cognition including attention capacity and impaired co-ordinative skills. Unsteadiness after takingbromazepam is, however, less pronounced than other benzodiazepines such as lorazepam. Impaired reactive andattention performance, which can impair driving skills.

Bromazepam 3

Drowsiness and decrease in libido. On occasion, benzodiazepines can induce extreme alterations in memory such asanterograde amnesia and amnesic automatism, which may have medico-legal consequences. Such reactions occurusually only at the higher dose end of the prescribing spectrum.Very rarely, dystonia can develop.Up to 30% treated on a long-term basis develop a form of dependence, i.e. these patients cannot stop the medicationwithout experiencing physical and/or psychological benzodiazepine withdrawal symptoms.Leukopenia and liver-damage of the cholostatic 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 operatemachinery. The impairment is worsened by consumption of alcohol, because both act as central nervous systemdepressants. During the course of therapy, tolerance to the sedative effect usually develops.

Tolerance, dependence and withdrawalBromazepam shares with other benzodiazepines the risk of abuse, misuse, psychological dependence and/or physicaldependence. A withdrawal study demonstrated both psychological dependence and physical dependence onbromazepam including marked rebound anxiety after 4 weeks chronic use. Those whose dose was gradually reducedexperienced no withdrawal.Patients treated with bromazepam for generalised anxiety disorder were found to experience withdrawal symptomssuch as a worsening of anxiety, as well as the development of physical withdrawal symptoms when abruptlywithdrawn bromazepam. Abrupt or over rapid withdrawal from bromazepam after chronic use even at therapeuticprescribed doses can lead to a severe withdrawal syndrome including status epilepticus and a condition resemblingdelerium tremens.Animal studies have shown that chronic administration of diazepam or bromazepam causes a decrease inspontaneous locomotor activity, decreased turnover of noradrenaline and dopamine and serotonin, increased activityof tyrosine hydroxylase and increased levels of the catecholamines. During withdrawal of bromazepam or diazepama fall in tryptophan, serotonin levels occurs as part of the benzodiazepine withdrawal syndrome. Changes in thelevels of these chemicals in the brain can cause headaches, anxiety, tension, depression, insomnia, restlessness,confusion, irritability, sweating, dysphoria, dizziness, derealization, depersonalization, numbness/tingling ofextremities, hypersensitivity to light, sound, and smell, perceptual distortions, nausea, vomiting, diarrhea, appetiteloss, hallucinations, delirium, seizures, tremor, stomach cramps, myalgia, agitation, palpitations, tachycardia, panicattacks, short-term memory loss, and hyperthermia.

Contraindications and special precautionsBenzodiazepines require special precaution if used in elderly, pregnant, child, alcohol- or drug-dependent individualsand individuals with comorbid psychiatric disorders.

Special populations• In 1987, a team of scientists led by Ochs reported that the elimination half-life, peak serum concentration, and

serum free fraction are significantly elevated and the oral clearance and volume of distribution significantlylowered in elderly subjects. The clinical consequence is that the elderly should be treated with lower doses thanyounger patients.

•• Bromazepam may affect driving and ability to operate machinery.• Bromazepam is pregnancy category D, a classification that means that bromazepam has been shown to cause

harm to the unborn child. The Hoffman LaRoche product information leaflet warns against breast feeding while

Bromazepam 4

taking bromazepam. There has been at least one report of sudden infant death syndrome linked to breast feedingwhile consuming bromazepam.

InteractionsCimetidine, fluvoxamine and propranolol causes a marked increase in the elimination half-life of bromazepamleading to increased accumulation of bromazepam.

Pharmacology

50 Pills of Lexotanil (containing 6 mg ofBromezepam apiece) as sold by Hoffmann-La

Roche in Germany

Bromazepam is a "classical" benzodiazepine; other classicalbenzodiazepines include; diazepam, clonazepam, oxazepam,lorazepam, nitrazepam, flurazepam, and clorazepate. Its molecularstructure is composed of a diazepine connected to a benzene ring and apyridine ring, the benzene ring having a bromine atom attached toit.[11] It is a 1,4-benzodiazepine, which means that the nitrogens on theseven-sided diazepine ring are in the 1 and 4 positions.

Bromazepam binds to the GABA receptor GABAA, causing aconformational change and increasing the inhibitory effects of GABA.Bromazepam is a long-acting benzodiazepine and is lipophilic andmetabolised hepatically via oxidative pathways. It does not possess anyantidepressant or antipsychotic qualities.

After night time administration of bromazepam a highly significantreduction of gastric acid secretion occurs during sleep followed by ahighly significant rebound in gastric acid production the following day.Bromazepam alters the electrical status of the brain causing an increasein beta activity and a decrease in alpha activity in EEG recordings.

PharmacokineticsBromazepam is reported to be metabolized by a hepatic enzyme belonging to the Cytochrome P450 family ofenzymes. In 2003, a team led by Dr. Oda Manami at Oita Medical University reported that CYP3A4, a member ofthe Cytochrome P450 family, was not the responsible enzyme since itraconazole, a known inhibitor of CYP3A4, didnot affect its metabolism.[12] In 1995, J. van Harten at Solvay Duphar B.V.'s Department of Clinical Pharmacologyin Weesp reported that fluvoxamine, which is a potent inhibitor of CYP1A2, a less potent CYP3A4 inhibitor, and anegligible inhibitor of CYP2D6, does inhibit its metabolism.The active metabolite of bromazepam is hydroxybromazepam, which has a half-life approximately equal to that ofbromazepam.Wikipedia:Citation needed

OverdoseMain article: Benzodiazepine overdoseBromazepam is commonly involved in drug overdoses. A severe bromazepam benzodiazepine overdose may resultin an alpha pattern coma type. The toxicity of bromazepam in overdosage increases when combined with other CNSdepressant drugs such as alcohol or sedative hypnotic drugs. Bromazepam is the most common benzodiazepineinvolved in intentional overdoses in France. Bromazepam has also been responsible for accidental poisonings incompanion animals. A review of benzodiazepine poisonings in cats and dogs from 1991-1994 found bromazepam tobe responsible for significantly more poisonings than any other benzodiazepine.

Bromazepam 5

Drug misuseSee also: Benzodiazepine drug misuseBromazepam has a similar misuse risk as other benzodiazepines such as diazepam. In France car accidents involvingpsychotropic drugs in combination found benzodiazepines, mainly diazepam, nordiazepam, and bromazepam, to bethe most common drug, almost twice that of the next-most-common drug cannabis. Bromazepam has also been usedfor serious criminal offences including robbery, homicide, and sexual assault.

Legal statusBromazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[13]

References[1] http:/ / www. drugs. com/ cons/ bromazepam. html[2] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2009/ MB_cgi?term=1812-30-2& rn=1[3] http:/ / www. whocc. no/ atc_ddd_index/ ?code=N05BA08[4] http:/ / pubchem. ncbi. nlm. nih. gov/ summary/ summary. cgi?cid=2441[5] http:/ / www. drugbank. ca/ drugs/ DB01558[6] http:/ / www. chemspider. com/ Chemical-Structure. 2347. html[7] http:/ / fdasis. nlm. nih. gov/ srs/ srsdirect. jsp?regno=X015L14V0O[8] http:/ / www. kegg. jp/ entry/ D01245[9] https:/ / www. ebi. ac. uk/ chembldb/ index. php/ compound/ inspect/ CHEMBL277062[10] http:/ / en. wikipedia. org/ w/ index. php?title=Special:ComparePages& rev1=413835339& page2=Bromazepam[11] Bromazepam (http:/ / www. eutimia. com/ psicofarmacos/ ansioliticos/ bromazepam. htm) Eutimia.com - Salud Mental. © 1999-2002.[12] 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. 2003 Nov;59(8-9):615-9. Epub 2003Sep 27. PMID 14517708 English Fulltext (registration required) (http:/ / dx. doi. org/ 10. 1007/ s00228-003-0681-4) Japanese Fulltext (PDF,no registration) (http:/ / www. oita-u. ac. jp/ gakui/ ik-307. pdf)

[13] List of psychotropic substances under international control (http:/ / www. incb. org/ pdf/ e/ list/ green. pdf) (PDF). International NarcoticsControl Board.

External links• Bromazepam drug information (http:/ / www. merck. com/ mmpe/ lexicomp/ bromazepam. html) from

Lexi-Comp. Includes dosage information and a comprehensive list of international brand names.• Inchem - Bromazepam (http:/ / www. inchem. org/ documents/ pims/ pharm/ pim281. htm)• LEXOTAN product information leaflet (http:/ / www. roche-australia. com/ downloads/ lexotan-pi.

cfm?action=get) from Roche Pharmaceuticals

Article Sources and Contributors 6

Article Sources and ContributorsBromazepam  Source: http://en.wikipedia.org/w/index.php?oldid=610352765  Contributors: 94peter, AManWithNoPlan, Adamantios, AioftheStorm, Anodyne, Arabhorse, Arcadian, Astavats,BalkanFever, Beetstra, Benjah-bmm27, Biruitorul, Boghog, Breno, Bryan Derksen, Calaschysm, Carlo Banez, Casforty, Chris the speller, Colin, Consequencefree, DendroNaja, DocWatson42,ESkog, Edgar181, Erik Kennedy, EtymAesthete, Fuzzform, Fvasconcellos, Gene Nygaard, Gjakova, Gor n bein, HalfFullGlass, Hehkuviini, Ian Pitchford, Ifnord, Ignacio Bibcraft, Ihaviman,Jared Preston, Johner, Kilom691, KirrVlad, LarryQ, Leyo, Lorien79, Louisajb, Maroboduus, Meodipt, Mr Bungle, MrADHD, Mykhal, Openandshutcase, Pashihiko, Petrb, Philip Trueman, R'n'B,R. S. Shaw, RDBrown, RJFJR, Remember me, Rich Farmbrough, Rjwilmsi, Rmky87, RonDivine, Sanaridas, Selket, Siva1979, Steve Bob, Vlad, WarFox, Westfall, Youniiiis, Zaiazepam, حسنanonymous edits 138 ,علي البط

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