2945 Diazepam Diazepam is 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). 439-14-5 3016 C16H13ClN2O 284.071640 White powder. 125-126°C 50 mg/L (at 25°C) Parenteral (intramuscular); oral; enteral(rectal).Essentially complete, with a bioavailability of 93%. 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. Hepatic via the Cytochrome P450 enzyme system. The main active metabolite is desmethyldiazepam, in addition to minor active metabolites including temazepam and oxazepam. Route of Elimination: Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates. Half Life: Biphasic 1-2 days and 2-5 days, active metabolites with long half lives. LD50: 1200 mg/kg (oral, rat) (L1862) LD50: 1000 mg/kg (oral, dog) (L1862) LD50: 700 mg/kg (oral, mice) (L1862) 3, not classifiable as to its carcinogenicity to humans. (L135) 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. They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. Symptoms of overdose include somnolence, confusion, coma, and diminished reflexes. Respiration, pulse and blood pressure should be monitored. General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. (L1712) 2009-07-21T20:27:45Z 2014-12-24T20:25:53Z Diazepam C06948 49575 Diazepam DB00829 DZP true CN1C2=C(C=C(Cl)C=C2)C(=NCC1=O)C1=CC=CC=C1 C16H13ClN2O InChI=1S/C16H13ClN2O/c1-19-14-8-7-12(17)9-13(14)16(18-10-15(19)20)11-5-3-2-4-6-11/h2-9H,10H2,1H3 InChIKey=AAOVKJBEBIDNHE-UHFFFAOYSA-N 284.74 284.071640755 Exogenous Solid 2.82 HMDB14967 CHEMBL12 2908 <p>Chase, G.; U.S. Patent 3,102,116; August 27, 1963; assigned to Hoffmann-La Roche Inc. Reeder, E. and Sternbach, L.H.; U.S. Patent 3,109,843; November 5, 1963; assigned to<br /> Hoffmann-La Roche lnc.<br /> Reeder, E. and Sternbach, L.H.; U.S. Patent 3,136,815; June 9, 1964; assigned to Hoffmann-<br /> La Roche Inc.<br /> Reeder, E. and Sternbach, L.H.; US. Patent 3,371,085; February 27, 1968; assigned to<br /> Hoffmann-La Roche Inc.</p>