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Identification
NameAdinazolam
Accession NumberDB00546  (APRD00724)
Typesmall molecule
Groups
Description

Adinazolam (Deracyn®) is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative, and antidepressant properties. Adinazolam was developed by Dr. Jackson B. Hester, who was seeking to enhance the antidepressant properties of alprazolam, which he also developed. Adinazolam was never FDA approved and was never available to the public.

Structure
Thumb
Synonyms
SynonymLanguageCode
AdinazolamumLatinINN
SaltsNot Available
Brand names
NameCompany
DeracynUpjohn
Brand mixturesNot Available
Categories
CAS number37115-32-5
WeightAverage: 351.833
Monoisotopic: 351.125073308
Chemical FormulaC19H18ClN5
InChI KeyInChIKey=GJSLOMWRLALDCT-UHFFFAOYSA-N
InChI
InChI=1S/C19H18ClN5/c1-24(2)12-18-23-22-17-11-21-19(13-6-4-3-5-7-13)15-10-14(20)8-9-16(15)25(17)18/h3-10H,11-12H2,1-2H3
IUPAC Name
({12-chloro-9-phenyl-2,4,5,8-tetraazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaen-3-yl}methyl)dimethylamine
SMILES
CN(C)CC1=NN=C2CN=C(C3=CC=CC=C3)C3=C(C=CC(Cl)=C3)N12
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzodiazepines
SubclassNot Available
Direct parentBenzodiazepines
Alternative parentsChlorobenzenes; Aryl Chlorides; Triazoles; Tertiary Amines; Polyamines; Organochlorides
Substituentschlorobenzene; aryl halide; aryl chloride; benzene; azole; 1,2,4-triazole; tertiary amine; polyamine; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
Pharmacology
IndicationFor the treatment of anxiety and status epilepticus.
PharmacodynamicsAdinazolam is a benzodiazepine derivative used to treat anxiety, status epilepticus, and for sedation induction and anterograde amnesia. Adinazolam binds with high affinity to the GABA benzodiazepine receptor complex. Considerable evidence suggest that the central pharmacologic/therapeutic actions of alprazolam are mediated via interaction with this receptor complex.
Mechanism of actionAdinazolam binds to peripheral-type benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic. The main metabolite is N-desmethyladinazolam. The other two metabolites are alpha-hydroxyalprazolam and estazolam.

SubstrateEnzymesProduct
Adinazolam
desmethyladinazolamDetails
Adinazolam
    EstazolamDetails
    Adinazolam
      alpha-HydroxyalprazolamDetails
      Route of eliminationNot Available
      Half lifeLess than 3 hours.
      ClearanceNot Available
      ToxicitySigns of overdose may include muscle weakness, ataxia, dysarthria and particularly in children paradoxical excitement. In more severe cases diminished reflexes, confusion, and coma may ensue.
      Affected organisms
      • Humans and other mammals
      PathwaysNot Available
      SNP Mediated EffectsNot Available
      SNP Mediated Adverse Drug ReactionsNot Available
      ADMET
      Predicted ADMET features
      Property Value Probability
      Human Intestinal Absorption + 1.0
      Blood Brain Barrier + 0.9382
      Caco-2 permeable + 0.6532
      P-glycoprotein substrate Substrate 0.666
      P-glycoprotein inhibitor I Inhibitor 0.5
      P-glycoprotein inhibitor II Inhibitor 0.942
      Renal organic cation transporter Inhibitor 0.8284
      CYP450 2C9 substrate Non-substrate 0.8375
      CYP450 2D6 substrate Non-substrate 0.9116
      CYP450 3A4 substrate Substrate 0.7407
      CYP450 1A2 substrate Inhibitor 0.6707
      CYP450 2C9 substrate Inhibitor 0.5
      CYP450 2D6 substrate Non-inhibitor 0.7089
      CYP450 2C19 substrate Non-inhibitor 0.6787
      CYP450 3A4 substrate Non-inhibitor 0.7326
      CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7718
      Ames test Non AMES toxic 0.8085
      Carcinogenicity Non-carcinogens 0.6543
      Biodegradation Not ready biodegradable 1.0
      Rat acute toxicity 2.6288 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.9259
      hERG inhibition (predictor II) Non-inhibitor 0.6971
      Pharmacoeconomics
      ManufacturersNot Available
      PackagersNot Available
      Dosage formsNot Available
      PricesNot Available
      PatentsNot Available
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      logP4.4Not Available
      Predicted Properties
      PropertyValueSource
      water solubility6.72e-02 g/lALOGPS
      logP2.57ALOGPS
      logP2.24ChemAxon
      logS-3.7ALOGPS
      pKa (strongest acidic)18.38ChemAxon
      pKa (strongest basic)6.66ChemAxon
      physiological charge0ChemAxon
      hydrogen acceptor count4ChemAxon
      hydrogen donor count0ChemAxon
      polar surface area46.31ChemAxon
      rotatable bond count3ChemAxon
      refractivity112.31ChemAxon
      polarizability37.15ChemAxon
      number of rings4ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis ReferenceNot Available
      General Reference
      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed
      3. File SE, Pellow S: Triazolobenzodiazepines antagonize the effects of anxiogenic drugs mediated at three different central nervous system sites. Neurosci Lett. 1985 Oct 24;61(1-2):115-9. Pubmed
      External Links
      ResourceLink
      KEGG DrugD02770
      PubChem Compound37632
      PubChem Substance46509054
      ChemSpider34519
      ChEBI251412
      ChEMBLCHEMBL328250
      Therapeutic Targets DatabaseDAP001251
      PharmGKBPA164783813
      WikipediaAdinazolam
      ATC CodesN05BA07
      AHFS CodesNot Available
      PDB EntriesNot Available
      FDA labelNot Available
      MSDSNot Available
      Interactions
      Drug InteractionsNot Available
      Food InteractionsNot Available

      1. Gamma-aminobutyric acid receptor subunit alpha-1

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      2. Gamma-aminobutyric acid receptor subunit alpha-2

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      3. Gamma-aminobutyric acid receptor subunit alpha-3

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      4. Gamma-aminobutyric acid receptor subunit alpha-5

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      5. Gamma-aminobutyric acid receptor subunit gamma-1

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      6. Gamma-aminobutyric acid receptor subunit gamma-2

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      7. Gamma-aminobutyric acid receptor subunit gamma-3

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      8. Gamma-aminobutyric acid receptor subunit beta-1

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      9. Gamma-aminobutyric acid receptor subunit beta-2

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      10. Gamma-aminobutyric acid receptor subunit beta-3

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      11. Gamma-aminobutyric acid receptor subunit delta

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit delta O14764 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      12. Gamma-aminobutyric acid receptor subunit epsilon

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit epsilon P78334 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      13. Gamma-aminobutyric acid receptor subunit pi

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit pi O00591 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      14. Gamma-aminobutyric acid receptor subunit rho-1

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit rho-1 P24046 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      15. Gamma-aminobutyric acid receptor subunit rho-2

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit rho-2 P28476 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      16. Gamma-aminobutyric acid receptor subunit rho-3

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit rho-3 A8MPY1 Details

      References:

      1. Lahti RA, Sethy VH, Barsuhn C, Hester JB: Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277-82. Pubmed
      2. Sethy VH, Collins RJ, Daniels EG: Determination of biological activity of adinazolam and its metabolites. J Pharm Pharmacol. 1984 Aug;36(8):546-8. Pubmed

      1. Cytochrome P450 2C19

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 2C19 P33261 Details

      References:

      1. Application available online: The P450 Program
      2. Venkatakrishnan K, von Moltke LL, Duan SX, Fleishaker JC, Shader RI, Greenblatt DJ: Kinetic characterization and identification of the enzymes responsible for the hepatic biotransformation of adinazolam and N-desmethyladinazolam in man. J Pharm Pharmacol. 1998 Mar;50(3):265-74. Pubmed
      3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

      2. Cytochrome P450 3A4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 3A4 P08684 Details

      References:

      1. Venkatakrishnan K, von Moltke LL, Duan SX, Fleishaker JC, Shader RI, Greenblatt DJ: Kinetic characterization and identification of the enzymes responsible for the hepatic biotransformation of adinazolam and N-desmethyladinazolam in man. J Pharm Pharmacol. 1998 Mar;50(3):265-74. Pubmed
      2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on February 18, 2014 21:37