Identification

Name
Azatadine
Accession Number
DB00719  (APRD00810)
Type
Small Molecule
Groups
Approved
Description

Antihistamines 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 IDs
Sch 10649 / UNII-94Z39NID6C / UNII-F3Q391WTX7
Product Ingredients
IngredientUNIICASInChI Key
Azatadine MaleateF3Q391WTX73978-86-7SGHXFFAHXTZRQM-SPIKMXEPSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Optimine Tab 1mgTablet1 mgOralSchering Plough1976-12-312009-08-04Canada
International/Other Brands
Idumed (NIHFI) / Optimine (Schering-Plough) / Zadine (Fulford)
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Trinalin RepetabsAzatadine Maleate (1 mg) + Pseudoephedrine sulfate (120 mg)Tablet, extended releaseOralSchering Plough1983-12-312007-08-03Canada
Categories
UNII
94Z39NID6C
CAS number
3964-81-6
Weight
Average: 290.4021
Monoisotopic: 290.178298714
Chemical Formula
C20H22N2
InChI Key
SEBMTIQKRHYNIT-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

Indication

For 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
Pharmacodynamics

Azatadine 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 action

Antihistamines 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.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Well absorbed after oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

The 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
Pathways
PathwayCategory
Azatadine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not 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
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
GepefrineGepefrine may decrease the sedative activities of Azatadine.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Azatadine.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Azatadine.Approved
Iofetamine I-123Iofetamine I-123 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
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Azatadine.Experimental
Midomafetamine3,4-Methylenedioxymethamphetamine may decrease the sedative activities of Azatadine.Experimental, Illicit, Investigational
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
Human Metabolome Database
HMDB14857
KEGG Compound
C07774
PubChem Compound
19861
PubChem Substance
46507958
ChemSpider
18709
BindingDB
22868
ChEBI
2946
ChEMBL
CHEMBL946
Therapeutic Targets Database
DAP001079
PharmGKB
PA164747157
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Azatadine
ATC Codes
R06AX09 — Azatadine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Schering corp sub schering plough corp
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral1 mg
Tablet, extended releaseOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)152-154REM 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 RuleNoChemAxon
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)

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

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzocycloheptapyridines
Sub Class
Not Available
Direct Parent
Benzocycloheptapyridines
Alternative Parents
Pyridines and derivatives / Piperidines / Benzenoids / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Benzocycloheptapyridine / Benzenoid / Pyridine / Piperidine / Heteroaromatic compound / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amine, benzocycloheptapyridine (CHEBI:2946)

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 catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:41