Identification

Name
Ethopropazine
Accession Number
DB00392  (APRD00729)
Type
Small Molecule
Groups
Approved
Description

Ethopropazine (also known as profenamine hydrochloride) is a medication derived from phenothiazine. It is primarily used as an antidyskinetic to treat parkinsonism. It is sold under the trade names Parsidol in the United States and Parsidan in Canada.

Structure
Thumb
Synonyms
  • 10-(2-Diethylaminopropyl)phenothiazine
  • 10-[2-(Diethylamino)-1-propyl]phenothiazine
  • 10-[2-(Diethylamino)-2-methylethyl]phenothiazine
  • 10-[2-(Diethylamino)propyl]phenothiazine
  • 2-Diethylamino-1-propyl-N-dibenzoparathiazine
  • Ethopropazine
  • N,N-Diethyl-1-(10H-phenothiazin-10-yl)-2-propanamine
  • N,N-Diethyl-alpha-methyl-10H-phenothiazine-10-ethanamine
  • Profenamina
  • Profenamine
  • Profenaminum
Product Ingredients
IngredientUNIICASInChI Key
Ethopropazine hydrochlorideO00T1I1VRN1094-08-2VXPCQISYVPFYRK-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Parsitan 50mgTablet50 mgOralErfa Canada 2012 Inc1952-12-31Not applicableCanada
International/Other Brands
Dibutil (Bayer) / Parkin (Tanabe) / Parsidan / Parsidol
Categories
UNII
7WI4P02YN1
CAS number
522-00-9
Weight
Average: 312.472
Monoisotopic: 312.166019468
Chemical Formula
C19H24N2S
InChI Key
CDOZDBSBBXSXLB-UHFFFAOYSA-N
InChI
InChI=1S/C19H24N2S/c1-4-20(5-2)15(3)14-21-16-10-6-8-12-18(16)22-19-13-9-7-11-17(19)21/h6-13,15H,4-5,14H2,1-3H3
IUPAC Name
diethyl[1-(10H-phenothiazin-10-yl)propan-2-yl]amine
SMILES
CCN(CC)C(C)CN1C2=CC=CC=C2SC2=CC=CC=C12

Pharmacology

Indication

For use in the treatment of Parkinson's disease and also used to control severe reactions to certain medicines such as reserpine.

Associated Conditions
Pharmacodynamics

Ethopropazine, a phenothiazine and antidyskinetic, is used in the treatment of Parkinson's disease. By improving muscle control and reducing stiffness, this drug permits more normal movements of the body as the disease symptoms are reduced. It is also used to control severe reactions to certain medicines such as reserpine, phenothiazines, chlorprothixene, thiothixene, loxapine, and haloperidol. Unlike other NMDA antagonists, ethopropazine — because of its anticholinergic action — is largely devoid of neurotoxic side effects. Ethopropazine also has a slight antihistaminic and local anesthetic effect.

Mechanism of action

Ethopropazine's antiparkinson action can be attributed to its anticholinergic properties. Ethopropazine partially blocks central (striatal) cholinergic receptors, thereby helping to balance cholinergic and dopaminergic activity in the basal ganglia; salivation may be decreased, and smooth muscle may be relaxed. Drug-induced extrapyramidal symptoms and those due to parkinsonism may be relieved, but tardive dyskinesia is not alleviated and may be aggravated by anticholinergic effects. Ethopropazine's local anesthetic effect is due to its antagonism of the NMDA glutamate receptor. Glutamate is recognized as an important transmitter in nociceptive pathways, and the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, in particular, has been implicated in the mediation of neuropathic pain. Excessive release of glutamate at NMDA receptors on dorsal horn neurons of the spinal cord results in hyperactivation and hypersensitivity of these receptors (perceived as hyperalgesia), thought to be an integral feature of neuropathic pain.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M1
antagonist
Human
AGlutamate receptor ionotropic, NMDA 3A
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
Absorption

Well-absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding

93%

Metabolism
Not Available
Route of elimination
Not Available
Half life

1 to 2 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include severe clumsiness or unsteadiness, severe drowsiness, severe dryness of mouth, nose, or throat, fast heartbeat, shortness of breath or troubled breathing, and warmth, dryness, and flushing of skin.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Ethopropazine can be decreased when used in combination with 1,10-Phenanthroline.
AclidiniumThe risk or severity of adverse effects can be increased when Ethopropazine is combined with Aclidinium.
AgmatineEthopropazine may increase the anticholinergic activities of Agmatine.
Ajulemic acidThe risk or severity of Tachycardia and drowsiness can be increased when Ethopropazine is combined with Ajulemic acid.
AlcuroniumEthopropazine may increase the anticholinergic activities of Alcuronium.
AlfentanilThe risk or severity of adverse effects can be increased when Ethopropazine is combined with Alfentanil.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Ethopropazine is combined with Alphacetylmethadol.
AlphaprodineThe risk or severity of adverse effects can be increased when Ethopropazine is combined with Alphaprodine.
Aluminum sulfateThe therapeutic efficacy of Aluminum sulfate can be decreased when used in combination with Ethopropazine.
AmbenoniumThe therapeutic efficacy of Ethopropazine can be decreased when used in combination with Ambenonium.
Food Interactions
Not Available

References

Synthesis Reference

Berg, S.S. and Ashley, J.N.; U.S. Patent 2,607,773; August 19,1952; assigned to Societe des Usines Chimiques Rhone-Poulenc, France.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014536
KEGG Drug
D01118
PubChem Compound
3290
PubChem Substance
46507375
ChemSpider
3174
BindingDB
8958
ChEBI
313639
ChEMBL
CHEMBL1206
Therapeutic Targets Database
DAP001119
PharmGKB
PA449531
Wikipedia
Ethopropazine
ATC Codes
N04AA05 — Profenamine
AHFS Codes
  • 28:36.08 — Anticholinergic Agents
  • 12:08.04 — Antiparkinsonian Agents
MSDS
Download (74 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableDYT 1 Dystonia / Primary Cervical Dystonia1

Pharmacoeconomics

Manufacturers
  • Parke davis div warner lambert co
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral50 mg
Prices
Unit descriptionCostUnit
Parsitan 50 mg Tablet0.23USD 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)166-168Berg, S.S. and Ashley, J.N.; U.S. Patent 2,607,773; August 19,1952; assigned to Societe des Usines Chimiques Rhone-Poulenc, France.
water solubility0.693 mg/LNot Available
logP5.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00524 mg/mLALOGPS
logP5.75ALOGPS
logP5ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)9.6ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity98 m3·mol-1ChemAxon
Polarizability36.34 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9898
Blood Brain Barrier+0.9915
Caco-2 permeable+0.766
P-glycoprotein substrateSubstrate0.8802
P-glycoprotein inhibitor IInhibitor0.8555
P-glycoprotein inhibitor IINon-inhibitor0.8161
Renal organic cation transporterNon-inhibitor0.5524
CYP450 2C9 substrateNon-substrate0.815
CYP450 2D6 substrateSubstrate0.7193
CYP450 3A4 substrateNon-substrate0.5838
CYP450 1A2 substrateInhibitor0.9108
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.885
CYP450 3A4 inhibitorNon-inhibitor0.8035
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6592
Ames testNon AMES toxic0.798
CarcinogenicityNon-carcinogens0.8551
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4696 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9544
hERG inhibition (predictor II)Inhibitor0.8448
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.73 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0udi-1900000000-add857d98ef29f21b7b8
GC-MS Spectrum - EI-BGC-MSsplash10-0udi-1900000000-31728da531ce58ffd47f
GC-MS Spectrum - CI-BGC-MSsplash10-0w29-2971000000-c72e808a24ef57c33eef
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, tertiary amino compound (CHEBI:313639)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. 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]
  2. Burke RE: The relative selectivity of anticholinergic drugs for the M1 and M2 muscarinic receptor subtypes. Mov Disord. 1986;1(2):135-44. [PubMed:2904117]
  3. Katayama S, Ishizaki F, Yamamura Y, Khoriyama T, Kito S: Effects of anticholinergic antiparkinsonian drugs on binding of muscarinic receptor subtypes in rat brain. Res Commun Chem Pathol Pharmacol. 1990 Sep;69(3):261-70. [PubMed:2236897]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein phosphatase 2a binding
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May ...
Gene Name
GRIN3A
Uniprot ID
Q8TCU5
Uniprot Name
Glutamate receptor ionotropic, NMDA 3A
Molecular Weight
125464.07 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. Jevtovic-Todorovic V, Meyenburg AP, Olney JW, Wozniak DF: Anti-parkinsonian agents procyclidine and ethopropazine alleviate thermal hyperalgesia in neuropathic rats. Neuropharmacology. 2003 May;44(6):739-48. [PubMed:12681372]
  4. Reynolds IJ, Miller RJ: [3H]MK801 binding to the N-methyl-D-aspartate receptor reveals drug interactions with the zinc and magnesium binding sites. J Pharmacol Exp Ther. 1988 Dec;247(3):1025-31. [PubMed:2849655]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Burke RE: The relative selectivity of anticholinergic drugs for the M1 and M2 muscarinic receptor subtypes. Mov Disord. 1986;1(2):135-44. [PubMed:2904117]
  2. Katayama S, Ishizaki F, Yamamura Y, Khoriyama T, Kito S: Effects of anticholinergic antiparkinsonian drugs on binding of muscarinic receptor subtypes in rat brain. Res Commun Chem Pathol Pharmacol. 1990 Sep;69(3):261-70. [PubMed:2236897]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Reiner E, Bosak A, Simeon-Rudolf V: Activity of cholinesterases in human whole blood measured with acetylthiocholine as substrate and ethopropazine as selective inhibitor of plasma butyrylcholinesterase. Arh Hig Rada Toksikol. 2004 Apr;55(1):1-4. [PubMed:15137175]
  2. Sinko G, Kovarik Z, Reiner E, Simeon-Rudolf V, Stojan J: Mechanism of stereoselective interaction between butyrylcholinesterase and ethopropazine enantiomers. Biochimie. 2011 Oct;93(10):1797-807. doi: 10.1016/j.biochi.2011.06.023. Epub 2011 Jun 29. [PubMed:21740955]

Drug created on June 13, 2005 07:24 / Updated on December 12, 2018 07:04