Identification

Name
Alimemazine
Accession Number
DB01246  (APRD00258)
Type
Small Molecule
Groups
Approved, Vet approved
Description

A phenothiazine derivative that is used as an antipruritic. [PubChem]

Structure
Thumb
Synonyms
  • Alimemazine
  • Methylpromazine
  • Repeltin
  • Trimeprazine
Product Ingredients
IngredientUNIICASInChI Key
Alimemazine tartrate362NW1LD6Z4330-99-8AJZJIYUOOJLBAU-RNKHSWPKSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Panectyl 2.5 Liq 2.5mg/5mlLiquid2.5 mgOralAventis Pharma Ltd.1960-12-312003-07-22Canada
Panectyl Tab 2.5mgTablet2.5 mgOralErfa Canada 2012 Inc1959-12-31Not applicableCanada
Panectyl Tab 5mgTablet5 mgOralErfa Canada 2012 Inc1959-12-31Not applicableCanada
International/Other Brands
Alimezine / Nedeltran / Panectyl / Theralen / Theralene / Vallergan
Categories
UNII
76H78MJJ52
CAS number
84-96-8
Weight
Average: 298.446
Monoisotopic: 298.150369404
Chemical Formula
C18H22N2S
InChI Key
ZZHLYYDVIOPZBE-UHFFFAOYSA-N
InChI
InChI=1S/C18H22N2S/c1-14(12-19(2)3)13-20-15-8-4-6-10-17(15)21-18-11-7-5-9-16(18)20/h4-11,14H,12-13H2,1-3H3
IUPAC Name
dimethyl[2-methyl-3-(10H-phenothiazin-10-yl)propyl]amine
SMILES
CC(CN(C)C)CN1C2=CC=CC=C2SC2=CC=CC=C12

Pharmacology

Indication

Used to prevent and relieve allergic conditions which cause pruritus (itching) and urticaria (some allergic skin reactions).

Associated Conditions
Pharmacodynamics

Trimeprazine (also known as Alimemazine) is a tricyclic antihistamine, similar in structure to the phenothiazine antipsychotics, but differing in the ring-substitution and chain characteristics. Trimeprazine is in the same class of drugs as chlorpromazine (Thorazine) and trifluoperazine (Stelazine); however, unlike the other drugs in this class, trimeprazine is not used clinically as an anti-psychotic. It acts as an anti-histamine, a sedative, and an anti-emetic (anti-nausea). Trimeprazine is used principally as an anti-emetic, to prevent motion sickness or as an anti-histamine in combination with other medications in cough and cold preparations. Tricyclic antihistamines are also structurally-related to the tricyclic antidepressants, explaining the antihistaminergic adverse effects of these two drug classes and also the poor tolerability profile of tricyclic H1-antihistamines.

Mechanism of action

Trimeprazine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Well absorbed in the digestive tract.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic

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

Symptoms of overdose 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
Alimemazine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Alimemazine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Alimemazine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Alimemazine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Alimemazine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Alimemazine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Alimemazine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Alimemazine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Alimemazine.
AbexinostatThe risk or severity of QTc prolongation can be increased when Alimemazine is combined with Abexinostat.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Alimemazine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015376
KEGG Compound
C07172
PubChem Compound
5574
PubChem Substance
46508449
ChemSpider
5373
BindingDB
50062261
ChEBI
9725
ChEMBL
CHEMBL829
Therapeutic Targets Database
DAP001077
PharmGKB
PA164744009
Wikipedia
Alimemazine
ATC Codes
R06AD01 — Alimemazine
AHFS Codes
  • 04:04.12 — Phenothiazine Derivatives

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Emcure Pharmaceuticals Ltd.
Dosage forms
FormRouteStrength
LiquidOral2.5 mg
TabletOral2.5 mg
TabletOral5 mg
Prices
Unit descriptionCostUnit
Panectyl 5 mg Tablet0.37USD tablet
Panectyl 2.5 mg Tablet0.3USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)68 °CPhysProp
boiling point (°C)150-175 °C at 3.00E-01 mm HgPhysProp
water solubility0.942 mg/LNot Available
logP4.71HANSCH,C ET AL. (1995)
pKa9.05SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.00835 mg/mLALOGPS
logP4.82ALOGPS
logP4.41ChemAxon
logS-4.6ALOGPS
pKa (Strongest Basic)9.42ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity93.37 m3·mol-1ChemAxon
Polarizability34.83 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9738
Blood Brain Barrier+0.9886
Caco-2 permeable+0.7965
P-glycoprotein substrateSubstrate0.6637
P-glycoprotein inhibitor IInhibitor0.6501
P-glycoprotein inhibitor IIInhibitor0.7613
Renal organic cation transporterNon-inhibitor0.5286
CYP450 2C9 substrateNon-substrate0.7739
CYP450 2D6 substrateSubstrate0.748
CYP450 3A4 substrateSubstrate0.5224
CYP450 1A2 substrateNon-inhibitor0.804
CYP450 2C9 inhibitorNon-inhibitor0.9195
CYP450 2D6 inhibitorInhibitor0.9381
CYP450 2C19 inhibitorNon-inhibitor0.8436
CYP450 3A4 inhibitorNon-inhibitor0.6702
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6487
Ames testNon AMES toxic0.7784
CarcinogenicityNon-carcinogens0.9034
BiodegradationNot ready biodegradable0.9968
Rat acute toxicity3.1217 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9819
hERG inhibition (predictor II)Inhibitor0.818
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.83 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4i-9010000000-3652afb69d877d9e3ef5
GC-MS Spectrum - EI-BGC-MSsplash10-0a4i-9240000000-3d6ddecfeef1ce4ea2a2
GC-MS Spectrum - CI-BGC-MSsplash10-0002-1192000000-93fd466d9dd2ccc3c679
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 / Benzenoids / 1,4-thiazines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Tertiary aliphatic/aromatic amine / Para-thiazine / Benzenoid / Tertiary amine / Tertiary aliphatic amine / Thioether
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines (CHEBI:9725)

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. Santos DE, Liu GJ, Takeuchi H: Blockers for excitatory effects of achatin-I, a tetrapeptide having a D-phenylalanine residue, on a snail neurone. Eur J Pharmacol. 1995 Jan 16;272(2-3):231-9. [PubMed:7713167]
  2. 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 September 23, 2018 19:37