Identification

Name
Methdilazine
Accession Number
DB00902  (APRD00713)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • Methdilazinum
  • Metodilazina
Product Ingredients
IngredientUNIICASInChI Key
Methdilazine HydrochlorideT0GSO02UEZ1229-35-2IEISBKIVLDXSMZ-UHFFFAOYSA-N
International/Other Brands
Dilosyn / Tacaryl
Categories
UNII
4Q13LY9Z8X
CAS number
1982-37-2
Weight
Average: 296.43
Monoisotopic: 296.13471934
Chemical Formula
C18H20N2S
InChI Key
HTMIBDQKFHUPSX-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

Pharmacology

Indication

Used for the symptomatic relief of hypersensitivity reactions and particularly for the control of pruritic skin disorders

Structured Indications
Not Available
Pharmacodynamics

In 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 action

Methdilazine 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.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Well absorbed in the digestive tract.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms 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
Pathways
PathwayCategory
Methdilazine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  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:15782943]
  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:9700532]
  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:2905130]
External Links
Human Metabolome Database
HMDB15038
KEGG Drug
D04979
KEGG Compound
C07175
PubChem Compound
14677
PubChem Substance
46505472
ChemSpider
14009
BindingDB
81470
ChEBI
6823
ChEMBL
CHEMBL1200959
Therapeutic Targets Database
DAP001070
PharmGKB
PA164743018
Wikipedia
Methdilazine
ATC Codes
R06AD04 — Methdilazine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Westwood squibb pharmaceuticals inc
  • Alpharma us pharmaceuticals division
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)87-88 °CPhysProp
water solubility0.348 mg/LNot Available
logP5.23HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0147 mg/mLALOGPS
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
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9901
Blood Brain Barrier+0.9949
Caco-2 permeable+0.7779
P-glycoprotein substrateSubstrate0.7768
P-glycoprotein inhibitor IInhibitor0.605
P-glycoprotein inhibitor IIInhibitor0.864
Renal organic cation transporterInhibitor0.834
CYP450 2C9 substrateNon-substrate0.7288
CYP450 2D6 substrateSubstrate0.7763
CYP450 3A4 substrateNon-substrate0.526
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorInhibitor0.9056
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9346
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6238
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9678
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity3.2306 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8634
hERG inhibition (predictor II)Inhibitor0.7305
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (11 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0002-9310000000-08a0f77b83bac7e129ee
Mass Spectrum (Electron Ionization)MSsplash10-0002-9630000000-8f3e969116ed3e70d7e5
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 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Alkyldiarylamines / Diarylthioethers / N-alkylpyrrolidines / Benzenoids / 1,4-thiazines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Tertiary aliphatic/aromatic amine / Para-thiazine / Benzenoid / N-alkylpyrrolidine / Pyrrolidine / Tertiary aliphatic amine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines (CHEBI:6823)

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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  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:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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:9700532]
  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. doi: 10.1007/s10096-009-0845-y. Epub 2009 Dec 13. [PubMed:20012879]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:15