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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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Aethopropropazin
  • Athapropazine
  • Athopropazin
  • Ethapropazine
  • Ethopromazine
  • Ethopropazine Hydrochloride
  • Etopropezina
  • Fempropazine
  • Fenpropazina
  • Isopthazine
  • Isotazin
  • Isothazine
  • Isothazine hydrochloride
  • Isothiazine
  • Phenopropazine
  • Phenoprozine
  • Prodierazine
  • Profenamina [INN-Spanish]
  • Profenamina [Italian]
  • Profenamine
  • Profenamine hydrochloride
  • Profenamine monohydrochloride
  • Profenaminum [INN-Latin]
  • Prophenamine
  • Prophenaminum
Brand names
  • Dibutil
  • Lysivane
  • Parcidol
  • Pardidol
  • Pardisol
  • Parfezin
  • Parfezine
  • Parkin
  • Parkisol
  • Parphezein
  • Parphezin
  • Parsidan
  • Parsidol
  • Parsitan
  • Parsotil
  • Prodictazin
  • Rochipel
  • Rocipel
  • Rodipal
  • Tomil
Brand name mixtures Not Available
Categories
  • Antiparkinson Agents
  • Antidyskinetics
CAS number 1094-08-2
Weight Average: 312.472
Monoisotopic: 312.166019468
Chemical Formula C19H24N2S
InChI Key InChIKey=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
Plain Text
IUPAC Name
diethyl[1-(10H-phenothiazin-10-yl)propan-2-yl]amine
SMILES
CCN(CC)C(C)CN1C2=C(SC3=C1C=CC=C3)C=CC=C2
Plain Text
Mass Spec show (7.7 KB)
Taxonomy
Kingdom Organic
Classes
  • Phenothiazines
Substructures
  • Ethers
  • Phenothiazines
  • Aliphatic and Aryl Amines
  • Thiazines
  • Benzene and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
Pharmacology
Indication For use in the treatment of Parkinson's disease and also used to control severe reactions to certain medicines such as reserpine.
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.
Absorption Well-absorbed from the gastrointestinal tract.
Volume of distribution Not Available
Protein binding 93%
Metabolism
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
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
Packagers Not Available
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Parsitan 50 mg Tablet 0.23 USD tablet
Patents Not Available
Properties
State solid
Melting point 64.5 oC
Experimental Properties
Property Value Source
water solubility 0.693 mg/L PhysProp
logP 5.2 PhysProp
Predicted Properties
Property Value Source
water solubility 5.24e-03 g/l ALOGPS
logP 5.75 ALOGPS
logP 5.00 ChemAxon Molconvert
logS -4.78 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 6.48 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 98.00 ChemAxon Molconvert
polarizability 36.34 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D01118 Link_out
PubChem Compound 3290 Link_out
PubChem Substance 46507375 Link_out
ChemSpider 3174 Link_out
BindingDB 8958 Link_out
ChEBI 313639 Link_out
ChEMBL 313639 Link_out
Therapeutic Targets Database DAP001119 Link_out
PharmGKB PA449531 Link_out
Drug Product Database 1927744 Link_out
Wikipedia http://en.wikipedia.org/wiki/Ethopropazine Link_out
ATC Codes
  • N04AA05
AHFS Codes
  • 12:08.04
PDB Entries Not Available
FDA label Not Available
MSDS show (74 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Muscarinic acetylcholine receptor M1

Pharmacological action: yes
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P11229 Link_out
Gene: CHRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Glutamate [NMDA] receptor subunit 3A

Pharmacological action: yes
Actions: antagonist

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 play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism

Organism class: human
UniProt ID: Q8TCU5 Link_out
Gene: GRIN3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. 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
  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

3. Muscarinic acetylcholine receptor M2

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition

Organism class: human
UniProt ID: P08172 Link_out
Gene: CHRM2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Enzymes

1. Cholinesterase

Actions: inhibitor

An acylcholine + H(2)O = choline + a carboxylate

UniProt ID: P06276 Link_out
Gene: BCHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Sinko G, Kovarik Z, Reiner E, Simeon-Rudolf V, Stojan J: Mechanism of stereoselective interaction between butyrylcholinesterase and ethopropazine enantiomers. Biochimie. 2011 Jun 29. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on August 03, 2011 08:55

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.