Azatadine

Identification

Summary

Azatadine is an H1 receptor antagonist used to treat perennial and allergic rhinitis as well as eustachian tube congestion.

Generic Name
Azatadine
DrugBank Accession Number
DB00719
Background

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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 290.4021
Monoisotopic: 290.178298714
Chemical Formula
C20H22N2
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

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.

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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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
Humans
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

Adverse Effects
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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.

Pathways
PathwayCategory
Azatadine H1-Antihistamine ActionDrug action
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
AcebutololThe risk or severity of QTc prolongation can be increased when Azatadine is combined with Acebutolol.
AcetazolamideThe therapeutic efficacy of Acetazolamide can be decreased when used in combination with Azatadine.
AcrivastineThe risk or severity of QTc prolongation can be increased when Azatadine is combined with Acrivastine.
AdenosineThe risk or severity of QTc prolongation can be increased when Azatadine is combined with Adenosine.
AjmalineThe risk or severity of QTc prolongation can be increased when Azatadine is combined with Ajmaline.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Azatadine.
AlimemazineThe risk or severity of QTc prolongation can be increased when Azatadine is combined with Alimemazine.
AmantadineThe risk or severity of QTc prolongation can be increased when Azatadine is combined with Amantadine.
AmifampridineThe risk or severity of seizure can be increased when Azatadine is combined with Amifampridine.
AmiodaroneThe risk or severity of QTc prolongation can be increased when Azatadine is combined with Amiodarone.
Interactions
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Food Interactions
  • Avoid alcohol.
  • Take with food. Food reduces irritation.

Products

Products
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Product Ingredients
IngredientUNIICASInChI Key
Azatadine maleateF3Q391WTX73978-86-7SGHXFFAHXTZRQM-SPIKMXEPSA-N
International/Other Brands
Idumed (NIHFI) / Optimine (Schering-Plough) / Zadine (Fulford)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Optimine Tab 1mgTablet1 mgOralSchering Plough1976-12-312009-08-04Canada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Trinalin RepetabsAzatadine maleate (1 mg) + Pseudoephedrine sulfate (120 mg)Tablet, extended releaseOralSchering Plough1983-12-312007-08-03Canada flag

Categories

ATC Codes
R06AX09 — Azatadine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Amine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzocycloheptapyridine / Heteroaromatic compound / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amine, benzocycloheptapyridine (CHEBI:2946)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
94Z39NID6C
CAS number
3964-81-6
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

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. [Article]
  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. [Article]
  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. [Article]
Human Metabolome Database
HMDB0014857
KEGG Compound
C07774
PubChem Compound
19861
PubChem Substance
46507958
ChemSpider
18709
BindingDB
22868
RxNav
18600
ChEBI
2946
ChEMBL
CHEMBL946
ZINC
ZINC000000968337
Therapeutic Targets Database
DAP001079
PharmGKB
PA164747157
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Azatadine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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

Targets

Drugtargets
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Kind
Protein
Organism
Humans
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. [Article]
  2. Mann KV, Crowe JP, Tietze KJ: Nonsedating histamine H1-receptor antagonists. Clin Pharm. 1989 May;8(5):331-44. [Article]
  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. [Article]
  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. [Article]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Kind
Protein
Organism
Humans
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. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]

Drug created on June 13, 2005 13:24 / Updated on May 06, 2021 01:41