Drug/Small Molecule:

diazepam

Overview

Generic Names:	DAP; Methyldiazepinone
IUPAC Name:	7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one
Trade Names:	Alboral; Aliseum; Alupram; Amiprol; An-Ding; Ansiolin; Ansiolisina; Apaurin; Apo-Diazepam; Apozepam; Armonil; Assival; Atensine; Atilen; Bensedin; Bialzepam; Calmocitene; Calmpose; Cercine; Ceregulart; Diacepan; Dialag; Dialar; Diapam; Diastat; Diazemuls; Diazemulus; Diazepam Intensol; Diazepan; Diazetard; Dienpax; Dipam; Dipezona; Dizac; Domalium; Duksen; Duxen; E-Pam; Eridan; Eurosan; Evacalm; Faustan; Faustan,; Freudal; Frustan; Gewacalm; Gihitan; Kabivitrum; Kiatrium; LA III; La-Iii; Lamra; Lembrol; Levium; Liberetas; Mandrozep; Morosan; Neurolytril; Noan; Novazam; Novo-Dipam; Paceum; Pacitran; Paranten; Paxate; Paxel; Plidan; Pms-Diazepam; Pro-Pam; Q-Pam; Q-Pam Relanium; Quetinil; Quiatril; Quievita; Relaminal; Relanium; Renborin; Ruhsitus; Saromet; Sedapam; Sedipam; Seduksen; Seduxen; Serenack; Serenamin; Serenzin; Servizepam; Setonil; Sibazon; Sibazone; Solis; Sonacon; Stesolid; Stesolin; Tensopam; Tranimul; Tranqdyn; Tranquase; Tranquirit; Tranquo-Puren; Tranquo-Tablinen; Umbrium; Unisedil; Usempax Ap; Valaxona; Valeo; Valiquid; Valitran; Valium; Valrelease; Vatran; Velium; Vival; Vivol; Zetran; Zipan
PharmGKB Accession Id:	PA449283

Description

A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity. It is used in the treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant, and in the management of alcohol withdrawal syndrome. (From Martindale, The Extra Pharmacopoeia, 30th ed, p589)

Indication

Used in the treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant, and in the management of alcohol withdrawal syndrome.

ATC Therapeutic Category

• N05BA:Benzodiazepine derivatives

Pharmacology and Interactions

Mechanism Of Action

Benzodiazepines bind nonspecifically to benzodiazepine receptors which mediate sleep, affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABA_A) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

Pharmacology

Diazepam, a benzodiazepine, generates the same active metabolite as chlordiazepoxide and clorazepate. In animals, diazepam appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. Diazepam, unlike chlorpromazine and reserpine, has no demonstrable peripheral autonomic blocking action, nor does it produce extrapyramidal side effects; however, animals treated with diazepam do have a transient ataxia at higher doses. Diazepam was found to have transient cardiovascular depressor effects in dogs. Long-term experiments in rats revealed no disturbances of endocrine function. Injections into animals have produced localized irritation of tissue surrounding injection sites and some thickening of veins after intravenous use.

Food Interactions

Avoid alcohol. Avoid excessive quantities of coffee or tea (caffeine). Avoid taking with grapefruit or grapefruit juice as grapefruit can significantly increase serum levels of this product. Take with food.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic via the Cytochrome P450 enzyme system. The main active metabolite is desmethyldiazepam, in addition to minor active metabolites including temazepam and oxazepam.

Protein Binding

98.5%

Absorption

Essentially complete, with a bioavailability of 93%.

Half Life

Biphasic 1-2 days and 2-5 days, active metabolites with long half lives.

Toxicity

Symptoms of overdose include somnolence, confusion, coma, and diminished reflexes. Respiration, pulse and blood pressure should be monitored.

Chemical Properties

Chemical Formula:

C₁₆H₁₃ClN₂O

SMILES Code:

CN1c2ccc(cc2C(=NCC1=O)c3ccccc3)Cl

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

284.74 / 284.0716

Curated Information

The following genes are in curated knowledge about this drug.

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

• CYP3A4
• CYP1A2

Drug Targets

• GABRA1
• GABRA3
• GABRA2
• TSPO

PharmGKB Curated Pathways

• Benzodiazepine pathway (PK)
• Benzodiazepinepathway (PD)

Curated Information

The following drugs are in curated knowledge about this drug.

	Drug	Relationship	Evidence
	fluoxetine	FA	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Anxiety Disorders	PD PK	Pathways
	Epilepsy	PD PK	Pathways
	Panic Disorder	PD PK	Pathways

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. Physicochemical determinants of human renal clearance

LinkOuts

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.