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Identification
NameMethdilazine
Accession NumberDB00902  (APRD00713)
TypeSmall Molecule
GroupsApproved
Description

Methdilazine is a phenothiazine compound with antihistaminic activity. It is used in the treatment of various dermatoses to relieve pruritus.

Structure
Thumb
Synonyms
SynonymLanguageCode
MethdilazinumLatinINN
MetodilazinaSpanishINN
TacarylNot AvailableNot Available
Salts
Name/CAS Structure Properties
Methdilazine Hydrochloride
Thumb
  • InChI Key: IEISBKIVLDXSMZ-UHFFFAOYNA-N
  • Monoisotopic Mass: 332.111397079
  • Average Mass: 332.891
DBSALT000486
Brand names
NameCompany
DilosynNot Available
TacarylNot Available
Brand mixturesNot Available
Categories
CAS number1982-37-2
WeightAverage: 296.43
Monoisotopic: 296.13471934
Chemical FormulaC18H20N2S
InChI KeyHTMIBDQKFHUPSX-UHFFFAOYSA-N
InChI
InChI=1S/C18H20N2S/c1-19-11-10-14(12-19)13-20-15-6-2-4-8-17(15)21-18-9-5-3-7-16(18)20/h2-9,14H,10-13H2,1H3
IUPAC Name
10-[(1-methylpyrrolidin-3-yl)methyl]-10H-phenothiazine
SMILES
CN1CCC(CN2C3=CC=CC=C3SC3=CC=CC=C23)C1
Mass Specshow(11 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzothiazines
SubclassPhenothiazines
Direct parentPhenothiazines
Alternative parentsBenzene and Substituted Derivatives; Pyrrolidines; Tertiary Amines; Polyamines; Thioethers
Substituentsbenzene; pyrrolidine; tertiary amine; polyamine; thioether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
Pharmacology
IndicationUsed for the symptomatic relief of hypersensitivity reactions and particularly for the control of pruritic skin disorders
PharmacodynamicsIn allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Methdilazine is a histamine H1 antagonist. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.
Mechanism of actionMethdilazine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.
AbsorptionWell absorbed in the digestive tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySymptoms of overdose include clumsiness or unsteadiness, convulsions, drowsiness, dryness of mouth, nose, or throat, feeling faint, flushing or redness of face, hallucinations, muscle spasms (especially of neck and back), restlessness, shortness of breath or troubled breathing, shuffling walk, tic-like movements of head and face, trembling and shaking of hands, and trouble in sleeping.
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 + 0.9901
Blood Brain Barrier + 0.9949
Caco-2 permeable + 0.7779
P-glycoprotein substrate Substrate 0.7768
P-glycoprotein inhibitor I Inhibitor 0.605
P-glycoprotein inhibitor II Inhibitor 0.864
Renal organic cation transporter Inhibitor 0.834
CYP450 2C9 substrate Non-substrate 0.7288
CYP450 2D6 substrate Substrate 0.7763
CYP450 3A4 substrate Non-substrate 0.526
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.9072
CYP450 2D6 substrate Inhibitor 0.9056
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.9346
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6238
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.9678
Biodegradation Not ready biodegradable 0.9972
Rat acute toxicity 3.2306 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8634
hERG inhibition (predictor II) Inhibitor 0.7305
Pharmacoeconomics
Manufacturers
  • Westwood squibb pharmaceuticals inc
  • Alpharma us pharmaceuticals division
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point87-88 °CPhysProp
water solubility0.348 mg/LNot Available
logP5.23HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0147ALOGPS
logP4.56ALOGPS
logP3.94ChemAxon
logS-4.3ALOGPS
pKa (Strongest Basic)8.81ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity91.64 m3·mol-1ChemAxon
Polarizability33.37 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
References
Synthesis ReferenceNot Available
General Reference
  1. Rani Basu L, Mazumdar K, Dutta NK, Karak P, Dastidar SG: Antibacterial property of the antipsychotic agent prochlorperazine, and its synergism with methdilazine. Microbiol Res. 2005;160(1):95-100. Pubmed
  2. Chattopadhyay D, Mukherjee T, Pal P, Saha B, Bhadra R: Altered membrane permeability as the basis of bactericidal action of methdilazine. J Antimicrob Chemother. 1998 Jul;42(1):83-6. Pubmed
  3. Chattopadhyay D, Dastidar SG, Chakrabarty AN: Antimicrobial properties of methdilazine and its synergism with antibiotics and some chemotherapeutic agents. Arzneimittelforschung. 1988 Jul;38(7):869-72. Pubmed
External Links
ResourceLink
KEGG DrugD04979
KEGG CompoundC07175
PubChem Compound14677
PubChem Substance46505472
ChemSpider14009
Therapeutic Targets DatabaseDAP001070
PharmGKBPA164743018
WikipediaMethdilazine
ATC CodesR06AD04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
BromocriptineThe phenothiazine decreases the effect of bromocriptine
CisaprideIncreased risk of cardiotoxicity and arrhythmias
DexfenfluramineDecreased anorexic effect, may increase psychotic symptoms
DiethylpropionDecreased anorexic effect, may increase psychotic symptoms
DonepezilPossible antagonism of action
FenfluramineDecreased anorexic effect, may increase psychotic symptoms
GalantaminePossible antagonism of action
GuanethidineMethdilazine may decrease the effect of guanethidine.
MazindolDecreased anorexic effect, may increase psychotic symptoms
PhentermineDecreased anorexic effect, may increase psychotic symptoms
PhenylpropanolamineDecreased anorexic effect, may increase psychotic symptoms
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
Food InteractionsNot Available

Targets

1. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  4. Chattopadhyay D, Mukherjee T, Pal P, Saha B, Bhadra R: Altered membrane permeability as the basis of bactericidal action of methdilazine. J Antimicrob Chemother. 1998 Jul;42(1):83-6. Pubmed
  5. Dasgupta A, Chaki S, Mukherjee S, Lourduraja J, Mazumdar K, Dutta NK, Dastidar SG: Experimental analyses of synergistic combinations of antibiotics with a recently recognised antibacterial agent, lacidipine. Eur J Clin Microbiol Infect Dis. 2010 Feb;29(2):239-43. Epub 2009 Dec 13. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12