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Identification
NameAzatadine
Accession NumberDB00719  (APRD00810)
TypeSmall Molecule
GroupsApproved
DescriptionAntihistamines such as azatadine appear to compete with histamine for histamine H1- receptor sites on effector cells. The antihistamines antagonize those pharmacological effects of histamine which are mediated through activation of H1- receptor sites and thereby reduce the intensity of allergic reactions and tissue injury response involving histamine release.
Structure
Thumb
Synonyms
11-(1-Methyl-4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
6,11-Dihydro-11-(1-methyl-4-piperidylidene)-5H-benzo(5,6)cyclohepta(1,2-b)pyridine
Azatadin
Azatadina
Azatadine
Azatadinum
External Identifiers
  • Sch 10649
  • UNII-94Z39NID6C
  • UNII-F3Q391WTX7
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Optimine Tab 1mgTablet1 mgOralSchering Plough Canada Inc1976-12-312009-08-04Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
IdumedNIHFI
OptimineSchering-Plough
ZadineFulford
Brand mixtures
NameLabellerIngredients
Trinalin RepetabsSchering Plough Canada Inc
Salts
Name/CASStructureProperties
Azatadine Maleate
ThumbNot applicableDBSALT000973
Categories
UNII94Z39NID6C
CAS number3964-81-6
WeightAverage: 290.4021
Monoisotopic: 290.178298714
Chemical FormulaC20H22N2
InChI KeySEBMTIQKRHYNIT-UHFFFAOYSA-N
InChI
InChI=1S/C20H22N2/c1-22-13-10-16(11-14-22)19-18-7-3-2-5-15(18)8-9-17-6-4-12-21-20(17)19/h2-7,12H,8-11,13-14H2,1H3
IUPAC Name
2-(1-methylpiperidin-4-ylidene)-4-azatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3(8),4,6,11,13-hexaene
SMILES
CN1CCC(CC1)=C1C2=CC=CC=C2CCC2=C1N=CC=C2
Pharmacology
IndicationFor the relief of the symptoms of upper respiratory mucosal congestion in perennial and allergic rhinitis, and for the relief of nasal congestion and eustachian t.b. congestion.
Structured Indications Not Available
PharmacodynamicsAzatadine is an antihistamine, related to cyproheptadine, with anti-serotonin, anticholinergic (drying), and sedative effects. Azatadine is in the same class of drugs as chlorpromazine (Thorazine) and trifluoperazine (Stelazine); however, unlike the other drugs in this class, azatadine is not used clinically as an anti-psychotic. Antihistamines antagonize the vasodilator effect of endogenously released histamine, especially in small vessels, and mitigate the effect of histamine which results in increased capillary permeability and edema formation. As consequences of these actions, antihistamines antagonize the physiological manifestations of histamine release in the nose following antigen-antibody interaction, such as congestion related to vascular engorgement, mucosal edema, and profuse, watery secretion, and irritation and sneezing resulting from histamine action on afferent nerve terminals.
Mechanism of actionAntihistamines such as azatadine appear to compete with histamine for histamine H1- receptor sites on effector cells. The antihistamines antagonize those pharmacological effects of histamine which are mediated through activation of H1- receptor sites and thereby reduce the intensity of allergic reactions and tissue injury response involving histamine release.
TargetKindPharmacological actionActionsOrganismUniProt ID
Histamine H1 receptorProteinyes
antagonist
HumanP35367 details
Related Articles
AbsorptionWell absorbed after oral administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityThe oral LD50 in mature rats and mice was greater than 1700 mg/kg and 600 mg/kg, respectively. Symptoms of overdose include clumsiness or unsteadiness, seizures, severe drowsiness, flushing or redness of face, hallucinations, muscle spasms (especially of neck and back), restlessness, shortness of breath, shuffling walk, tic-like (jerky) movements of head and face, trembling and shaking of hands, and insomnia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Azatadine.Experimental, Illicit
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Azatadine.Experimental, Illicit
3,4-Methylenedioxymethamphetamine3,4-Methylenedioxymethamphetamine may decrease the sedative activities of Azatadine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Azatadine.Experimental, Illicit
AmphetamineAmphetamine may decrease the sedative activities of Azatadine.Approved, Illicit
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Azatadine.Approved, Investigational
BenzphetamineBenzphetamine may decrease the sedative activities of Azatadine.Approved, Illicit
Benzylpenicilloyl PolylysineAzatadine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Azatadine.Approved
ChlorphentermineChlorphentermine may decrease the sedative activities of Azatadine.Illicit, Withdrawn
DextroamphetamineDextroamphetamine may decrease the sedative activities of Azatadine.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Azatadine.Approved, Illicit
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Azatadine.Approved, Investigational
Hydroxyamphetamine hydrobromideHydroxyamphetamine hydrobromide may decrease the sedative activities of Azatadine.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Azatadine.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Azatadine.Investigational
MephentermineMephentermine may decrease the sedative activities of Azatadine.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Azatadine.Approved, Illicit
MMDAMMDA may decrease the sedative activities of Azatadine.Experimental, Illicit
PhenterminePhentermine may decrease the sedative activities of Azatadine.Approved, Illicit
PseudoephedrinePseudoephedrine may decrease the sedative activities of Azatadine.Approved
RitobegronRitobegron may decrease the sedative activities of Azatadine.Investigational
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Azatadine.Approved
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.
References
Synthesis Reference

Raymond E. Dagger, Linda A. Motyka, “Process for preparing intermediates for azatidine.” U.S. Patent US4954632, issued September 04, 1990.

US4954632
General References
  1. Zhang D, Hansen EB Jr, Deck J, Heinze TM, Sutherland JB, Cerniglia CE: Fungal biotransformation of the antihistamine azatadine by Cunninghamella elegans. Appl Environ Microbiol. 1996 Sep;62(9):3477-9. [PubMed:8795241 ]
  2. Katelaris C: Comparative effects of loratadine and azatadine in the treatment of seasonal allergic rhinitis. Asian Pac J Allergy Immunol. 1990 Dec;8(2):103-7. [PubMed:1982614 ]
  3. Small P, Barrett D, Biskin N: Effects of azatadine, terfenadine, and astemizole on allergen-induced nasal provocation. Ann Allergy. 1990 Feb;64(2 Pt 1):129-31. [PubMed:1968324 ]
External Links
ATC CodesR06AX09
AHFS Codes
  • 04:04.92
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9973
Blood Brain Barrier+0.9826
Caco-2 permeable+0.7341
P-glycoprotein substrateSubstrate0.8357
P-glycoprotein inhibitor IInhibitor0.9232
P-glycoprotein inhibitor IIInhibitor0.545
Renal organic cation transporterInhibitor0.8115
CYP450 2C9 substrateNon-substrate0.8064
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5716
CYP450 1A2 substrateNon-inhibitor0.5801
CYP450 2C9 inhibitorNon-inhibitor0.791
CYP450 2D6 inhibitorInhibitor0.6078
CYP450 2C19 inhibitorNon-inhibitor0.8348
CYP450 3A4 inhibitorNon-inhibitor0.835
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6425
Ames testNon AMES toxic0.7616
CarcinogenicityNon-carcinogens0.9692
BiodegradationNot ready biodegradable0.9819
Rat acute toxicity2.9760 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.804
hERG inhibition (predictor II)Inhibitor0.6909
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Schering corp sub schering plough corp
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral1 mg
Tablet, extended releaseOral
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point152-154REM p. 1131 Villani, F.J.; U.S. Patents 3,326,924; January 20, 1967; 3,357,986; December 12, 1967; and 3,419,565; December 31,1968; all assigned to Schering Corp.
water solubilityVery solubleNot Available
logP3.59BIOBYTE (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.113 mg/mLALOGPS
logP3.67ALOGPS
logP3.75ChemAxon
logS-3.4ALOGPS
pKa (Strongest Basic)7.91ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area16.13 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity101.53 m3·mol-1ChemAxon
Polarizability34.01 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzocycloheptapyridines. These are aromatic compounds containing a benzene ring and a pyridine ring fused to a seven membered carbocycle.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzocycloheptapyridines
Sub ClassNot Available
Direct ParentBenzocycloheptapyridines
Alternative Parents
Substituents
  • Benzocycloheptapyridine
  • Benzenoid
  • Pyridine
  • Piperidine
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
References
  1. Singh N, Puri SK: Causal prophylactic activity of antihistaminic agents against Plasmodium yoelii nigeriensis infection in Swiss mice. Acta Trop. 1998 Jun;69(3):255-60. [PubMed:9638277 ]
  2. Mann KV, Crowe JP, Tietze KJ: Nonsedating histamine H1-receptor antagonists. Clin Pharm. 1989 May;8(5):331-44. [PubMed:2568212 ]
  3. Clissold SP, Sorkin EM, Goa KL: Loratadine. A preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs. 1989 Jan;37(1):42-57. [PubMed:2523301 ]
  4. Haria M, Fitton A, Peters DH: Loratadine. A reappraisal of its pharmacological properties and therapeutic use in allergic disorders. Drugs. 1994 Oct;48(4):617-37. [PubMed:7528133 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23