12-chloro-3-methyl-9-phenyl-2,4,5,8-tetraazatricyclo[8.4.0.02,6]tetradeca-1(10),3,5,8,11,13-hexaene

• ChemBase ID: 287
• Molecular Formular: C17H13ClN4
• Molecular Mass: 308.76492
• Monoisotopic Mass: 308.08287412
• SMILES: Clc1cc2c(n3c(nnc3C)CN=C2c2ccccc2)cc1
• Canonical SMILES: Clc1ccc2c(c1)C(=NCc1n2c(C)nn1)c1ccccc1
• InChI: InChI=1S/C17H13ClN4/c1-11-20-21-16-10-19-17(12-5-3-2-4-6-12)14-9-13(18)7-8-15(14)22(11)16/h2-9H,10H2,1H3
• InChIKey: VREFGVBLTWBCJP-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 12-chloro-3-methyl-9-phenyl-2,4,5,8-tetraazatricyclo[8.4.0.0^2,^6]tetradeca-1(10),3,5,8,11,13-hexaene; 12-chloro-3-methyl-9-phenyl-2,4,5,8-tetraazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene; 12-chloro-3-methyl-9-phenyl-2,4,5,8-tetraazatricyclo[8.4.0.0^2,^6]tetradeca-1(14),3,5,8,10,12-hexaene
• IUPAC Traditional name: 12-chloro-3-methyl-9-phenyl-2,4,5,8-tetraazatricyclo[8.4.0.0^2,^6]tetradeca-1(10),3,5,8,11,13-hexaene; neurol; alprazolam
• Brand Name: Alplax; Alpronax; Alviz; Bestrol; Cassadan; Constan; D 65MT; Esparon; Frontal; Intensol; Niravam; Restyl; Solanax; Tafil; Tranax; Trankimazin; Tranquinal; Xanax; Xanax XR; Xanor
• Synonyms: Niravam; 8-chloro-1-methyl-6-phenyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine; Alprazolam solution; TUS-1; alprazolam; Alprazolam; D-65MT; U-31889; Alplax; Cassadan; Esparon; Tafil; Tranquinal; Xanax; 8-Chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine; Alprazolam; 阿普唑仑 溶液; 阿普唑仑

Database IDs

• CAS Number: 28981-97-7
• EC Number: 200-659-6; 249-349-2
• MDL Number: MFCD00078881
• PubChem SID: 160963750; 24882050; 24891366; 46507078
• PubChem CID: 2118
• CHEBI ID: 2611
• ATC CODE: N05BA12
• CHEMBL: 661
• Chemspider ID: 2034
• DrugBank ID: DB00404
• KEGG ID: D00225
• Unique Ingredient Identifier: YU55MQ3IZY
• Wikipedia Title: Alprazolam
• Medline Plus: a684001

CALCULATED PROPERTIES

JChem

• Acid pKa: 18.299637
• H Acceptors: 3
• H Donor: 0
• LogD (pH = 5.5): 2.2350945
• LogD (pH = 7.4): 2.3720427
• Log P: 2.3741
• Molar Refractivity: 98.879 cm^3
• Polarizability: 33.40099 Å^3
• Polar Surface Area: 43.07 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.23
• LOG S: -3.98
• Solubility (Water): 3.24e-02 g/l

PROPERTIES

Physical Property

• Solubility: 40 mg/L at pH 7; 12 mg/mL at pH 1.2; H2O: insoluble; Methanol; methanol: soluble
• Apperance: White Solid
• Melting Point: 228-2290C
• Hydrophobicity(logP): 4.9

Safety Information

• Storage Condition: Controlled Substance, -20°C Freezer
• RTECS: XZ5473000
• European Hazard Symbols: Flammable (F); Toxic (T); Harmful (Xn)
• UN Number: 1230
• German water hazard class: 1; 3
• Hazard Class: 3
• Packing Group: 2
• Risk Statements: 11-23/24/25-39/23/24/25; 22
• Safety Statements: 36; 7-16-36/37-45
• GHS Pictograms: GHS06; GHS07; GHS08
• GHS Signal Word: Danger; Warning
• GHS Hazard statements: H301-H311-H331-H370; H302
• GHS Precautionary statements: P260-P280-P301 + P310-P311
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves; Eyeshields, Faceshields, full-face respirator (US), Gloves, multi-purpose combination respirator cartridge (US), type ABEK (EN14387) respirator filter
• RID/ADR: UN 1230 3/PG 2
• Drug Control: kontrollierte Droge in Deutschlandregulated under CDSA - not available from Sigma-Aldrich Canada; USDEA Schedule IV; Home Office Schedule 4.1; psychotrope; kontrollierte Droge in Deutschland; regulated under CDSA - not available from Sigma-Aldrich Canada
• Storage Temperature: -20°C

Pharmacology Properties

• Admin Routes: Oral
• Bioavailability: 80–90%
• Excretion: Renal
• Half Life: Extended release: 10.7–15.8 hours; Immediate release: 11.2 hours
• Metabolism: Hepatic, via Cytochrome P450 3A4
• Legal Status: POM (UK); Schedule IV (US)
• Pregnancy Category: D (US)
• Mechanism of Action: Benzodiazepine receptor agonist

Product Information

• Concentration: 1 mg/mL in methanol
• Grade: analytical standard, for drug analysis
• Application(s): Muscle relaxant; Psychosedative; Tranquilliser
• Empirical Formula (Hill Notation): C17H13ClN4

DETAILS

DrugBank - DB00404

• Drug Groups: illicit; approved; investigational
• Description: A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of panic disorders, with or without agoraphobia, and in generalized anxiety disorders. (From AMA Drug Evaluations Annual, 1994, p238)
• Indication: For the management of anxiety disorder or the short-term relief of symptoms of anxiety and for the treatment of panic disorder, with or without agoraphobia.
• Pharmacology: Alprazolam, a benzodiazepine, is used to treat panic disorder and anxiety disorder. Unlike chlordiazepoxide, clorazepate, and prazepam, alprazolam has a shorter half-life and metabolites with minimal activity. Like other triazolo benzodiazepines such as triazolam, alprazolam may have significant drug interactions involving the hepatic cytochrome P-450 3A4 isoenzyme. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis. Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking.
• Toxicity: Oral, mouse: LD₅₀=1020 mg/kg. Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Hydroxylated in the liver to α-hydroxyalprazolam, which is also active. This and other metabolites are later excreted in urine as glucuronides.
• Absorption: Readily absorbed from the gastrointestinal tract. Bioavailability is 80-90%.
• Half Life: 6.3-26.9 hours
• Protein Binding: 80% (mainly to albumin)
• Elimination: Alprazolam and its metabolites are excreted primarily in the urine.
• Clearance: * 2.13 +/- 0.54 mL/min/kg [CYP3A inducers]; * 0.90 +/- 0.21 mL/min/kg [without CYP3A inducers]
• References: Risse SC, Whitters A, Burke J, Chen S, Scurfield RM, Raskind MA: Severe withdrawal symptoms after discontinuation of alprazolam in eight patients with combat-induced posttraumatic stress disorder. J Clin Psychiatry. 1990 May;51(5):206-9. [Pubmed] ; Wolf B, Griffiths RR: Physical dependence on benzodiazepines: differences within the class. Drug Alcohol Depend. 1991 Dec 31;29(2):153-6. [Pubmed] ; Haque W, Watson DJ, Bryant SG: Death following suspected alprazolam withdrawal seizures: a case report. Tex Med. 1990 Jan;86(1):44-7. [Pubmed] ; Hori A: Pharmacotherapy for personality disorders. Psychiatry Clin Neurosci. 1998 Feb;52(1):13-9. [Pubmed] ; Garcia-Algar O, Lopez-Vilchez MA, Martin I, Mur A, Pellegrini M, Pacifici R, Rossi S, Pichini S: Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis. Clin Toxicol (Phila). 2007;45(3):295-8. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Sigma Aldrich - A8800

Biochem/physiol Actions
Benzodiazepine anxiolytic; ligand for the GABAA receptor benzodiazepine modulatory site.

Toronto Research Chemicals - A575650

Controlled substance (depressant). Anxiolytic.

REFERENCES

• Wolf B, Griffiths RR: Physical dependence on benzodiazepines: differences within the class. Drug Alcohol Depend. 1991 Dec 31;29(2):153-6. Pubmed
• Haque W, Watson DJ, Bryant SG: Death following suspected alprazolam withdrawal seizures: a case report. Tex Med. 1990 Jan;86(1):44-7. Pubmed
• Hori A: Pharmacotherapy for personality disorders. Psychiatry Clin Neurosci. 1998 Feb;52(1):13-9. Pubmed
• Garcia-Algar O, Lopez-Vilchez MA, Martin I, Mur A, Pellegrini M, Pacifici R, Rossi S, Pichini S: Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis. Clin Toxicol (Phila). 2007;45(3):295-8. Pubmed
• Risse SC, Whitters A, Burke J, Chen S, Scurfield RM, Raskind MA: Severe withdrawal symptoms after discontinuation of alprazolam in eight patients with combat-induced posttraumatic stress disorder. J Clin Psychiatry. 1990 May;51(5):206-9. Pubmed
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