2901 Midazolam A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. [PubChem] Midazolam is a schedule IV drug in the United States. 59467-70-8 4192 C18H13ClFN3 325.078200 White powder. 159°C 0.024 mg/mL Rapidly absorbed after oral administration. The absolute bioavailability of the midazolam syrup in pediatric patients is about 36%. The absolute bioavailability, if given intramuscularly (IM), is greater than 90%. Cmax, IM = 90 ng/mL; Tmax, IM = 0.5 hours. Following IM administered, Cmax for midazolam and its 1-hydroxy metabolite were approxiately one-half of those achieved after intravenous injection. It is thought that the actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the brain. Benzodiazepines increase the activity of GABA, thereby producing a calming effect, relaxing skeletal muscles, and inducing sleep. Benzodiazepines act as agonists at the benzodiazepine receptors, which form a component of the benzodiazepine-GABA receptor-chloride ionophore complex. Most anxiolytics appear to act through at least one component of this complex to enhance the inhibitory action of GABA. Midazolam is primarily metabolized in the liver and gut by human cytochrome P450 IIIA4 (CYP3A4) to its pharmacologic active metabolite, (alpha)-hydroxymidazolam (also known as 1-hydroxy-midazolam), and 4-hydroxymidazolam (makes up 5% or less of the biotransformation products). 1-hydroxy-midazolam is at least as potent as the parent compound and may contributed to the overall activity of midazolam. In vitro studies have demonstrated that the affinities of 1- and 4-hydroxy-midazolam for the benzodiazepine receptor are approximately 20% and 7%, respectively, relative to midazolam. It also undergoes N-glucuronidation via UGT1A4. Route of Elimination: Midazolam is primarily metabolized in the liver and gut by human cytochrome P450 IIIA4 (CYP3A4) to its pharmacologic active metabolite, alpha-hydroxymidazolam, followed by glucuronidation of the alpha-hydroxyl metabolite which is present in unconjugated and conjugated forms in human plasma. The alpha- hydroxymidazolam glucuronide is then excreted in urine. No significant amount of parent drug or metabolites is extractable from urine before beta-glucuronidase and sulfatase deconjugation, indicating that the urinary metabolites are excreted mainly as conjugates. The amount of midazolam excreted unchanged in the urine when given intravenously is less than 0.5%. 45% to 57% of the dose was excreted in the urine as 1-hydroxymethyl midazolam conjugate. Half Life: Intravenous, healthy adults = 1.8 to 6.4 hours (mean of 3 hours) LD50: 825 mg/kg (Oral, Rat) No indication of carcinogenicity to humans (not listed by IARC). Intravenous midazolam is indicated for procedural sedation (often in combination with an opioid, such as fentanyl), for pre-op sedation, for the induction of general anesthesia, and for sedation of ventilated patients in critical care units. Oral midazolam is indicated for the short term treatment of moderately severe insomnia in patients who did not adequately react to other hypnotics, and who have persistent trouble in falling asleep. [Wikipedia] They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. Treatment of midazolam overdosage is the same as that followed for overdosage with other benzodiazepines. Respiration, pulse rate and blood pressure should be monitored and general supportive measures should be employed. Attention should be given to the maintenance of a patent airway and support of ventilation, including administration of oxygen. Should hypotension develop, treatment may include intravenous fluid therapy, repositioning, judicious use of vasopressors appropriate to the clinical situation, if indicated, and other appropriate counter-measures. Gastrointestinal decontamination with lavage and/or activated charcoal once the patient's airway is secure is also recommended. Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of midazolam and may be used in situations when an overdose with a benzodiazepine is known or suspected. (L1712) 2009-07-21T20:27:24Z 2026-03-26T18:33:06Z Midazolam C07524 127611 Midazolam DB00683 08J true CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12 C18H13ClFN3 InChI=1S/C18H13ClFN3/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13/h2-9H,10H2,1H3 DDLIGBOFAVUZHB-UHFFFAOYSA-N 325.767 325.078203343 Exogenous Solid HMDB14821 CHEMBL655 4047 <p>Madhup K. Dhaon, &#8220;Process for the preparation of midazolam.&#8221; U.S. Patent US6262260, issued August, 1979.</p> CHEM002247 DTXSID5023320 NS00000476 12-chloro-9-(2-fluorophenyl)-3-methyl-2,4,8-triazatricyclo[8.4.0.0²,⁶]tetradeca-1(10),3,5,8,11,13-hexaene