3065 Estazolam Estazolam is only found in individuals that have used or taken this drug. It is a benzodiazepine with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam. [PubChem] Benzodiazepines bind nonspecifically to benzodiazepine receptors, which affects 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 GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell. 29975-16-4 3261 C16H11ClN4 294.067220 White powder. 228-229°C Practically insoluble (1.5 mg/L) Tablets have been found to be equivalent in absorption to an orally administered solution of estazolam. In healthy subjects who received up to three times the recommended dose, peak estazolam plasma concentrations occurred within two hours after dosing (range 0.5 to 6.0 hours) and were proportional to the administered dose, suggesting linear pharmacokinetics over the dosage range tested. Benzodiazepines bind nonspecifically to benzodiazepine receptors, which affects 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 GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell. Extensively metabolized in the liver. In vitro studies with human liver microsomes indicate that the biotransformation of estazolam to the major circulating metabolite 4-hydroxy-estazolam is mediated by cytochrome P450 3A (CYP3A). Route of Elimination: Estazolam is extensively metabolized. The elimination of the parent drug takes place via hepatic metabolism of estazolam to hydroxylated and other metabolites that are eliminated largely in the urine both free and conjugated. Less than 5% of a 2 mg dose of estazolam was excreted unchanged in the urine, with only 4% of the dose appearing in the feces. Radiolabel mass balance studies indicate that the main route of excretion is via the kidneys. After 5 days, 87% of the administered radioactivity was excreted in human urine. Less than 4% of the dose was excreted unchanged. Half Life: The range of estimates for the mean elimination half-life of estazolam varies from 10 to 24 hours. LD50: 740 mg/kg (oral, male mice) (L1867) LD50: 3200 mg/kg (oral, rat) (L1867) LD50 300 mg/kg (oral, rabbit) (L1867) 3, not classifiable as to its carcinogenicity to humans. (L135) For the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. 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 confusion, depressed breathing, drowsiness and eventually coma, lack of coordination, and slurred speech. Gastric evacuation, either by the induction of emesis, lavage, or both, should be performed immediately. Maintenance of adequate ventilation is essential. General supportive care, including frequent monitoring of the vital signs and close observation of the patient, is indicated. Fluids should be administered intravenously to maintain blood pressure and encourage diuresis. The value of dialysis in treatment of benzodiazepine overdose has not been determined. The physician may wish to consider contacting a Poison Control Center for up-to-date information on the management of hypnotic drug product overdose. 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) 2009-07-21T20:28:39Z 2014-12-24T20:25:56Z Estazolam 4858 Estazolam DB01215 true ClC1=CC2=C(C=C1)N1C=NN=C1CN=C2C1=CC=CC=C1 C16H11ClN4 InChI=1S/C16H11ClN4/c17-12-6-7-14-13(8-12)16(11-4-2-1-3-5-11)18-9-15-20-19-10-21(14)15/h1-8,10H,9H2 InChIKey=CDCHDCWJMGXXRH-UHFFFAOYSA-N 294.738 294.067224079 Exogenous Solid 4.7 HMDB15346 CHEMBL1201169 3146 <p>Hester, J.B. Jr.; U.S. Patent 3,701,782; October 31, 1972; assigned to The Upjohn Co.</p>