Identification

Name
Isothipendyl
Accession Number
DB08802
Type
Small Molecule
Groups
Approved
Description

Isothipendyl is an antihistamine and anticholinergic used as an antipruritic.

Structure
Thumb
Synonyms
  • Actapront
Product Ingredients
IngredientUNIICASInChI Key
Isothipendyl hydrochloride953AP1LBV81225-60-1RQHCFTORMXCNGP-UHFFFAOYSA-N
International/Other Brands
Actapront (Purissimus) / Alergis Jalea (Deutsche Pharma) / Andantol (Deutsche Pharma) / Apaisyl (Merck) / Calmogel (Sanofi) / Nilergex (I.C.I.)
Categories
UNII
WVZ7K9P0JY
CAS number
482-15-5
Weight
Average: 285.407
Monoisotopic: 285.129968313
Chemical Formula
C16H19N3S
InChI Key
OQJBSDFFQWMKBQ-UHFFFAOYSA-N
InChI
InChI=1S/C16H19N3S/c1-12(18(2)3)11-19-13-7-4-5-8-14(13)20-15-9-6-10-17-16(15)19/h4-10,12H,11H2,1-3H3
IUPAC Name
dimethyl(1-{9-thia-2,4-diazatricyclo[8.4.0.0³,⁸]tetradeca-1(14),3(8),4,6,10,12-hexaen-2-yl}propan-2-yl)amine
SMILES
CC(CN1C2=CC=CC=C2SC2=C1N=CC=C2)N(C)C

Pharmacology

Indication

For the topical treatment of itching associated with allergic reactions.

Pharmacodynamics

Isothipendyl, an azaphenothiazine derivative, competitively binds to histamine (H1) receptors, resulting in inhibition of the pharmacological effects of histamines. It also has some sedative, anticholinergic and antiserotoninergic effects.

Mechanism of action

Isothipendyl is a selective histamine H1 antagonist and 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
Not Available
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
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Isothipendyl 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 Isothipendyl.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Isothipendyl.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Isothipendyl.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Isothipendyl.Experimental, Illicit
AmphetamineAmphetamine may decrease the sedative activities of Isothipendyl.Approved, Illicit, Investigational
BenzphetamineBenzphetamine may decrease the sedative activities of Isothipendyl.Approved, Illicit
Benzylpenicilloyl PolylysineIsothipendyl may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Isothipendyl.Approved, Investigational
ChlorphentermineChlorphentermine may decrease the sedative activities of Isothipendyl.Illicit, Withdrawn
DextroamphetamineDextroamphetamine may decrease the sedative activities of Isothipendyl.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Isothipendyl.Approved, Illicit
GepefrineGepefrine may decrease the sedative activities of Isothipendyl.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Isothipendyl.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Isothipendyl.Approved
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Isothipendyl.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Isothipendyl.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Isothipendyl.Investigational
MephentermineMephentermine may decrease the sedative activities of Isothipendyl.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Isothipendyl.Approved, Illicit
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Isothipendyl.Experimental
MidomafetamineMidomafetamine may decrease the sedative activities of Isothipendyl.Experimental, Illicit, Investigational
MMDAMMDA may decrease the sedative activities of Isothipendyl.Experimental, Illicit
PhenterminePhentermine may decrease the sedative activities of Isothipendyl.Approved, Illicit
PseudoephedrinePseudoephedrine may decrease the sedative activities of Isothipendyl.Approved
RitobegronRitobegron may decrease the sedative activities of Isothipendyl.Investigational
Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 2,974,139.

General References
  1. Moreau A, Dompmartin A, Dubreuil A, Leroy D: Phototoxic and photoprotective effects of topical isothipendyl. Photodermatol Photoimmunol Photomed. 1995 Apr;11(2):50-4. [PubMed:8546983]
External Links
Human Metabolome Database
HMDB0015692
KEGG Drug
D08091
PubChem Compound
3781
PubChem Substance
99445272
ChemSpider
3649
ChEBI
135183
ChEMBL
CHEMBL2111066
PharmGKB
PA165958421
Wikipedia
Isothipendyl
ATC Codes
D04AA22 — IsothipendylR06AD09 — Isothipendyl

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)213-216U.S. Patent 2,974,139.
Predicted Properties
PropertyValueSource
Water Solubility0.14 mg/mLALOGPS
logP3.45ALOGPS
logP3.66ChemAxon
logS-3.3ALOGPS
pKa (Strongest Basic)8.91ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area19.37 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity86.66 m3·mol-1ChemAxon
Polarizability31.9 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9928
Blood Brain Barrier+0.9804
Caco-2 permeable+0.808
P-glycoprotein substrateSubstrate0.7871
P-glycoprotein inhibitor IInhibitor0.6515
P-glycoprotein inhibitor IINon-inhibitor0.655
Renal organic cation transporterInhibitor0.5198
CYP450 2C9 substrateNon-substrate0.7399
CYP450 2D6 substrateSubstrate0.7027
CYP450 3A4 substrateSubstrate0.5135
CYP450 1A2 substrateInhibitor0.9167
CYP450 2C9 inhibitorNon-inhibitor0.88
CYP450 2D6 inhibitorInhibitor0.7844
CYP450 2C19 inhibitorNon-inhibitor0.8657
CYP450 3A4 inhibitorNon-inhibitor0.8468
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5185
Ames testNon AMES toxic0.8079
CarcinogenicityNon-carcinogens0.9305
BiodegradationNot ready biodegradable0.993
Rat acute toxicity2.5794 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9751
hERG inhibition (predictor II)Inhibitor0.7695
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
GC-MS Spectrum - EI-BGC-MSsplash10-00di-9000000000-fcb41271c0640c5ac2b5
GC-MS Spectrum - CI-BGC-MSsplash10-000i-7090000000-32a33b7c7fcd9798b725
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 alkyldiarylamines. These are tertiary alkylarylamines having two aryl and one alkyl groups attached to the amino group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Alkyldiarylamines
Alternative Parents
Diarylthioethers / Benzothiazines / Pyridines and derivatives / Imidolactams / Benzenoids / 1,4-thiazines / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds
show 1 more
Substituents
Alkyldiarylamine / Diarylthioether / Benzothiazine / Aryl thioether / Para-thiazine / Pyridine / Benzenoid / Imidolactam / Heteroaromatic compound / Tertiary aliphatic amine
show 6 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

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. Moreau A, Dompmartin A, Dubreuil A, Leroy D: Phototoxic and photoprotective effects of topical isothipendyl. Photodermatol Photoimmunol Photomed. 1995 Apr;11(2):50-4. [PubMed:8546983]

Drug created on October 15, 2010 10:26 / Updated on June 02, 2018 09:32