Bromazepam

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Bromazepam
Systematic (IUPAC) name
9-bromo-6-pyridin-2-yl- 2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraen-3-one
Identifiers
CAS number	1812-30-2
ATC code	N05BA08
PubChem	2441
DrugBank	?
Chemical data
Formula	C₁₄H₁₀Br N₃O
Mol. mass	316.2
Pharmacokinetic data
Bioavailability	84%
Metabolism	Hepatic
Half life	10-20 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	D (USA)
Legal status	Schedule IV(US)
Routes	Oral

Bromazepam (marketed under brand names Calmepam, Compendium, Creosedin, Durazanil, Lectopam, Lexaurin, Lexomil, Lexotan, Lexotanil, Normoc, Somalium)^[1] is a drug which is a benzodiazepine derivative. It has sedative, hypnotic, anxiolytic and skeletal muscle relaxant properties.

1 Pharmacology
2 Indications
- 2.1 Availability
3 Dosage
4 Side-effects
5 Contraindications
- 5.1 Special Populations
6 Legal Status
7 References
8 External links

[edit] Pharmacology

Its molecular structure is composed of a diazepine connected to two benzene rings, one of which has a bromine atom attached to it.^[2] 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 inhibitory effects of GABA. Other neurotransmitters are not influenced. It does not possess any antidepressant qualities. Bromazepam shares with other benzodiazepines the risk of abuse, misuse, psychological and/or physical dependence. According to many psychiatric experts Bromazepam has a greater abuse potential than other benzodiazepines because of fast resorption and rapid onset of action. Due to its relatively short halflife and duration of action (8 to 12 hours), withdrawal symptoms may be more severe and more frequently encountered than with long acting benzodiazepines.

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 was not the responsible enzyme, seeing as itraconazole, a known inhibitor of CYP3A4, did not effect its metabolism.^[3] 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.^[4]

The active metabolite of bromazepam is hydroxybromazepam.

[edit] Indications

Short-term treatment of insomnia
Short-term treatment of anxiety or panic attacks, if a benzodiazepine is required
Alleviation of the symptoms of alcohol- and opiate-withdrawal, under close clinical supervision

[edit] Availability

Bromazepam is available as a generic in Canada, Germany, The Netherlands, Italy, France, Macedonia, Portugal, Kosovo, Switzerland. It is also available in the United Arab Emirates, Pakistan, Venezuela and Columbia in the form of Lexotanil and in Brazil, Singapore and Portugal in the form of Lexotan and Somalium.

[edit] Dosage

Usually, 3mg to 6mg at bedtime, with additional 1.5mg to 3mg during the next day if needed. Malnourished patients, patients with compromised cardiovascular, liver or renal function, and elderly patients should receive lower doses. In hospitalized patients with severe agitation and/or anxiety, daily doses of up to 24mg have been given and tolerated for a limited period of time. A 3mg dose of bromazepam is equivalent to a 5mg dose of diazepam.

[edit] Side-effects

All common side-effects of benzodiazepines have been noted. Consult the article under Diazepam. Euphoria, leading to a high abuse potential, is quite often reported.

Up to 30% treated on a long-term basis develop a form of dependence known as 'low-dose-dependence', i.e. these patients do not need increasing doses to experience the feeling of 'well-being' caused by the drug.

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.

[edit] Contraindications

The general contraindications for benzodiazepines apply. Consult the section under Diazepam.

[edit] Special Populations

In 1987, a team of scientists lead 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.^[5] The clinical consequence is that the elderly should be treated with lower doses than younger patients.

[edit] Legal Status

Bromazepam is a Schedule IV drug under the Convention on Psychotropic Substances.^[6]

[edit] References

^ PubChem Substance: Bromazepam National Center of Biotechnology Information.
^ 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) Japanese Fulltext (PDF, no registration)
^ van Harten J. "Overview of the pharmacokinetics of fluvoxamine." Clinical Pharmacokinetics. 1995;29 Suppl 1:1-9. PMID 8846617
^ 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 & Therapeutics. 1987 May;41(5):562-70. PMID 2882883
^ List of psychotropic substances under international control (PDF). International Narcotics Control Board.