Identification

Name
Adinazolam
Accession Number
DB00546
Description

Adinazolam (Deracyn®) is a benzodiazepine derivative with anxiolytic, anticonvulsant, sedative, and antidepressant properties. Adinazolam was first developed to enhance the antidepressant effects of alprazolam. It has never been approved by the FDA for clinical use.

Type
Small Molecule
Groups
Experimental
Structure
Thumb
Weight
Average: 351.833
Monoisotopic: 351.125073308
Chemical Formula
C19H18ClN5
Synonyms
  • 8-Chloro-1-((dimethylamino)methyl)-6-phenyl-4H-s-triazolo(4,3-a)(1,4)benzodiazepine
  • Adinazolam
  • Adinazolamum
External IDs
  • U-41,123
  • U-41123

Pharmacology

Indication

For the treatment of anxiety and status epilepticus.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Adinazolam 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 action

Adinazolam 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.

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

The drug primarily undergoes hepatic metabolism to form the main metabolite N-desmethyladinazolam, alpha-hydroxyalprazolam, and estazolam.

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Route of elimination
Not Available
Half-life

Less than 3 hours.

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Signs 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Adinazolam can be increased when it is combined with Abametapir.
AcenocoumarolThe risk or severity of adverse effects can be increased when Adinazolam is combined with Acenocoumarol.
AcetazolamideThe risk or severity of adverse effects can be increased when Adinazolam is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Adinazolam is combined with Acetophenazine.
AclidiniumAdinazolam may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Adinazolam is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Adinazolam.
AlimemazineThe risk or severity of adverse effects can be increased when Adinazolam is combined with Alimemazine.
AlmotriptanThe risk or severity of adverse effects can be increased when Adinazolam is combined with Almotriptan.
AlosetronThe risk or severity of adverse effects can be increased when Adinazolam is combined with Alosetron.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

Product Ingredients
IngredientUNIICASInChI Key
Adinazolam mesylateNT8S62A72757938-82-6FENBITQPWFCMEB-UHFFFAOYSA-N
International/Other Brands
Deracyn (Upjohn)

Categories

ATC Codes
N05BA07 — Adinazolam
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 1,2,4-triazolo[4,3-a][1,4]benzodiazepines. These are aromatic compounds containing a 1,4-benzodiazepine fused to and sharing a nitrogen atom with a 1,2,4-triazole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
1,2,4-triazolo[4,3-a][1,4]benzodiazepines
Alternative Parents
Aralkylamines / Benzene and substituted derivatives / Aryl chlorides / Triazoles / Heteroaromatic compounds / Trialkylamines / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organopnictogen compounds
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Substituents
1,2,4-triazole / 1,2,4-triazolo[4,3-a][1,4]benzodiazepine / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Benzenoid
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
triazolobenzodiazepine (CHEBI:251412)

Chemical Identifiers

UNII
KN08449444
CAS number
37115-32-5
InChI Key
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[8.4.0.0²,⁶]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

References

General 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:6320036]
  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:6148400]
  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:2867497]
Human Metabolome Database
HMDB0014686
KEGG Drug
D02770
PubChem Compound
37632
PubChem Substance
46509054
ChemSpider
34519
BindingDB
82439
ChEBI
251412
ChEMBL
CHEMBL328250
ZINC
ZINC000004214740
Therapeutic Targets Database
DAP001251
PharmGKB
PA164783813
Wikipedia
Adinazolam

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, extended releaseOral1000 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0672 mg/mLALOGPS
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 Area46.31 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity112.31 m3·mol-1ChemAxon
Polarizability37.15 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9382
Caco-2 permeable+0.6532
P-glycoprotein substrateSubstrate0.666
P-glycoprotein inhibitor IInhibitor0.5
P-glycoprotein inhibitor IIInhibitor0.942
Renal organic cation transporterInhibitor0.8284
CYP450 2C9 substrateNon-substrate0.8375
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateInhibitor0.6707
CYP450 2C9 inhibitorInhibitor0.5
CYP450 2D6 inhibitorNon-inhibitor0.7089
CYP450 2C19 inhibitorNon-inhibitor0.6787
CYP450 3A4 inhibitorNon-inhibitor0.7326
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7718
Ames testNon AMES toxic0.8085
CarcinogenicityNon-carcinogens0.6543
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6288 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9259
hERG inhibition (predictor II)Non-inhibitor0.6971
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [PubMed:23038269]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [PubMed:29950725]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
Curator comments
Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [PubMed:23038269]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [PubMed:29950725]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
There are limited data in the literature regarding this enzyme action.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
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:9600717]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
There are limited data in the literature regarding this enzyme action.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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:9600717]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2020 03:03

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