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 C
14
H
10
BrN
3
O
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 Roche
in 1963 and developed clinically in the 1970s. It has mainly an anti-anxiety agent with similar side effects to
diazepam (Valium). 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 3mg and 6mg tablets. Bromazepam is
contraindicated and should be used with caution in women who are pregnant, the elderly, patients with a history of
alcohol or other substance abuse disorders and children. Prolonged use of bromazepam causes 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.
Indications
Short-term treatment of anxiety or panic attacks, if a benzodiazepine is required.
Premedication to alleviate anxiety before surgery.
Side-effects
Bromazepam causes similar side effects to other benzodiazepines. The most common side effects reported are
drowsiness, sedation, ataxia, memory impairment, and dizziness. Impairments to memory functions are common
with 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 learning
capacity observed that taking Bromazepam alone at 6mg 3 times daily for 2 weeks impaired learning capacities
significantly. 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 taking
bromazepam is, however, less pronounced than other benzodiazepines such as lorazepam. Impaired reactive and
attention performance, which can impair driving skills.
Bromazepam
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Drowsiness and decrease in libido. 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.
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 medication
without 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 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.
Tolerance, dependence and withdrawal
Bromazepam shares with other benzodiazepines the risk of abuse, misuse, psychological dependence and/or physical
dependence. 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.
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. 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.
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. 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.
Contraindications and special precautions
Benzodiazepines require special precaution if used in elderly, pregnant, child, alcohol- or drug-dependent individuals
and 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 significantly
lowered in elderly subjects. The clinical consequence is that the elderly should be treated with lower doses than
younger 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 feeding
while consuming bromazepam.
Interactions
Cimetidine, fluvoxamine and propranolol causes a marked increase in the elimination half-life of bromazepam
leading to increased accumulation of bromazepam.
Pharmacology
50 Pills of Lexotanil (containing 6 mg of
Bromezepam apiece) as sold by Hoffmann-La
Roche in Germany
Bromazepam is a "classical" benzodiazepine; other classical
benzodiazepines include; diazepam, clonazepam, oxazepam,
lorazepam, nitrazepam, flurazepam, and clorazepate. Its molecular
structure is composed of a diazepine connected to a benzene ring and a
pyridine ring, the benzene ring having a bromine atom attached to
it.
[11]
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 GABA
A
, causing a
conformational change and increasing the inhibitory effects of GABA.
Bromazepam is a long-acting benzodiazepine and is lipophilic and
metabolised hepatically via oxidative pathways. It does not possess any
antidepressant or antipsychotic qualities.
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.
Bromazepam alters the electrical status of the brain causing an increase
in beta activity and a decrease in alpha activity in EEG recordings.
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 Dr. 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.
[12]
In 1995, J. van Harten at Solvay Duphar B.V.'s 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 active metabolite of bromazepam is hydroxybromazepam, which has a half-life approximately equal to that of
bromazepam.Wikipedia:Citation needed
Overdose
Main article: Benzodiazepine overdose
Bromazepam is commonly involved in drug overdoses. A severe bromazepam benzodiazepine overdose may result
in an alpha pattern coma type. The toxicity of bromazepam in overdosage increases when combined with other CNS
depressant drugs such as alcohol or sedative hypnotic drugs. Bromazepam is the most common benzodiazepine
involved in intentional overdoses in France. Bromazepam has also been responsible for accidental poisonings in
companion animals. A review of benzodiazepine poisonings in cats and dogs from 1991-1994 found bromazepam to
be responsible for significantly more poisonings than any other benzodiazepine.
Bromazepam
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Drug misuse
See also: Benzodiazepine drug misuse
Bromazepam has a similar misuse risk as other benzodiazepines such as diazepam. In France car accidents involving
psychotropic drugs in combination found benzodiazepines, mainly diazepam, nordiazepam, and bromazepam, to be
the most common drug, almost twice that of the next-most-common drug cannabis. Bromazepam has also been used
for serious criminal offences including robbery, homicide, and sexual assault.
Legal status
Bromazepam 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 2003
Sep 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 Narcotics
Control 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 Contributors
Bromazepam 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,
, 138 anonymous edits
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