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Identification
NameEthopropazine
Accession NumberDB00392  (APRD00729)
TypeSmall Molecule
GroupsApproved
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
SynonymLanguageCode
10-(2-Diethylaminopropyl)phenothiazineNot AvailableNot Available
10-[2-(Diethylamino)-1-propyl]phenothiazineNot AvailableNot Available
10-[2-(Diethylamino)-2-methylethyl]phenothiazineNot AvailableNot Available
10-[2-(Diethylamino)propyl]phenothiazineNot AvailableNot Available
2-Diethylamino-1-propyl-N-dibenzoparathiazineNot AvailableNot Available
EthopropazineNot AvailableNot Available
N,N-Diethyl-1-(10H-phenothiazin-10-yl)-2-propanamineNot AvailableNot Available
N,N-Diethyl-alpha-methyl-10H-phenothiazine-10-ethanamineNot AvailableNot Available
ProfenaminaSpanishINN
ProfenamineNot AvailableINN
ProfenaminumLatinINN
Salts
Name/CAS Structure Properties
Ethopropazine Hydrochloride
Thumb
  • InChI Key: VXPCQISYVPFYRK-UHFFFAOYNA-N
  • Monoisotopic Mass: 348.142697207
  • Average Mass: 348.933
DBSALT000813
Brand names
NameCompany
DibutilBayer
ParkinTanabe
ParsidanNot Available
ParsidolNot Available
Brand mixturesNot Available
Categories
CAS number1094-08-2
WeightAverage: 312.472
Monoisotopic: 312.166019468
Chemical FormulaC19H24N2S
InChI KeyCDOZDBSBBXSXLB-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
Mass Specshow(7.73 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzothiazines
SubclassPhenothiazines
Direct parentPhenothiazines
Alternative parentsBenzene and Substituted Derivatives; Tertiary Amines; Polyamines; Thioethers
Substituentsbenzene; tertiary amine; thioether; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the 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.
Pharmacology
IndicationFor use in the treatment of Parkinson's disease and also used to control severe reactions to certain medicines such as reserpine.
PharmacodynamicsEthopropazine, 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 actionEthopropazine'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.
AbsorptionWell-absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein binding93%
Metabolism
Route of eliminationNot Available
Half life1 to 2 hours
ClearanceNot Available
ToxicitySymptoms 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9898
Blood Brain Barrier + 0.9915
Caco-2 permeable + 0.766
P-glycoprotein substrate Substrate 0.8802
P-glycoprotein inhibitor I Inhibitor 0.8555
P-glycoprotein inhibitor II Non-inhibitor 0.8161
Renal organic cation transporter Non-inhibitor 0.5524
CYP450 2C9 substrate Non-substrate 0.815
CYP450 2D6 substrate Substrate 0.7193
CYP450 3A4 substrate Non-substrate 0.5838
CYP450 1A2 substrate Inhibitor 0.9108
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.8931
CYP450 2C19 substrate Non-inhibitor 0.885
CYP450 3A4 substrate Non-inhibitor 0.8035
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6592
Ames test Non AMES toxic 0.798
Carcinogenicity Non-carcinogens 0.8551
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.4696 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9544
hERG inhibition (predictor II) Inhibitor 0.8448
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Parsitan 50 mg Tablet0.23USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point166-168Berg, 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 Solubility0.00524ALOGPS
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
Spectra
SpectraNot 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 ReferenceNot Available
External Links
ResourceLink
KEGG DrugD01118
PubChem Compound3290
PubChem Substance46507375
ChemSpider3174
BindingDB8958
ChEBI313639
ChEMBLCHEMBL1206
Therapeutic Targets DatabaseDAP001119
PharmGKBPA449531
Drug Product Database1927744
WikipediaEthopropazine
ATC CodesN04AA05
AHFS Codes
  • 12:08.04
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(74 KB)
Interactions
Drug Interactions
Drug
BromocriptineThe phenothiazine decreases the effect of bromocriptine
CisaprideIncreased risk of cardiotoxicity and arrhythmias
DexfenfluramineDecreased anorexic effect, may increase psychotic symptoms
DiethylpropionDecreased anorexic effect, may increase psychotic symptoms
DonepezilPossible antagonism of action
FenfluramineDecreased anorexic effect, may increase psychotic symptoms
GalantaminePossible antagonism of action
GuanethidineEthopropazine may decrease the effect of guanethidine.
HaloperidolThe anticholinergic increases the risk of psychosis and tardive dyskinesia
MazindolDecreased anorexic effect, may increase psychotic symptoms
PhentermineDecreased anorexic effect, may increase psychotic symptoms
PhenylpropanolamineDecreased anorexic effect, may increase psychotic symptoms
Food InteractionsNot Available

Targets

1. Muscarinic acetylcholine receptor M1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

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 receptor ionotropic, NMDA 3A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 3A Q8TCU5 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cholinesterase P06276 Details

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

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Drug created on June 13, 2005 07:24 / Updated on April 22, 2014 10:31