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Details

Stereochemistry ABSOLUTE
Molecular Formula C12H15NO3S
Molecular Weight 253.317
Optical Activity ( + )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Thiorphan, (S)-

SMILES

OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1

InChI

InChIKey=LJJKNPQAGWVLDQ-SNVBAGLBSA-N
InChI=1S/C12H15NO3S/c14-11(15)7-13-12(16)10(8-17)6-9-4-2-1-3-5-9/h1-5,10,17H,6-8H2,(H,13,16)(H,14,15)/t10-/m1/s1

HIDE SMILES / InChI
Ecadotril or sinorphan is the S-enantiomer of racemic acetorphan (racecadotril). It inhibits enkephalinase activity. Ecadotril was studied for the treatment of hypertension and heart failure, however, its development was discontinued.

CNS Activity

Curator's Comment: Ecadotril ((S)-acetorphan) is CNS active in animals when administered parenterally. No human data available.

Originator

Curator's Comment: Roques, B. P., Schwartz, J. C. & Lecomte, J. M., inventors. Derives d'acides amines et leur application therapeutique. Fr. Pat. 8008601, Apr. 17, 1980; Eur. Pat. Appl. EP 38,758; Apr. 14, 1981.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
400 mg 2 times / day multiple, oral (max)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1142
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: Cardiac Failure Congestive
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources: Page: p.1142
Other AEs: Headache, Dizziness...
Other AEs:
Headache (16%)
Dizziness (grade 1-2, 35%)
Insomnia (6%)
Sources: Page: p.1142
AEs

AEs

AESignificanceDosePopulation
Headache 16%
400 mg 2 times / day multiple, oral (max)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1142
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: Cardiac Failure Congestive
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources: Page: p.1142
Insomnia 6%
400 mg 2 times / day multiple, oral (max)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1142
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: Cardiac Failure Congestive
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources: Page: p.1142
Dizziness grade 1-2, 35%
400 mg 2 times / day multiple, oral (max)
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1142
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: Cardiac Failure Congestive
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources: Page: p.1142
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice.
1980 Nov 20
Thiorphan potentiation of stress-induced analgesia in the mouse.
1982 Sep 20-27
Complete differentiation between enkephalinase and angiotensin-converting enzyme inhibition by retro-thiorphan.
1983 Jun
Pharmacological properties of acetorphan, a parenterally active "enkephalinase" inhibitor.
1986 Jun
Naloxone-reversible antidiarrheal effects of enkephalinase inhibitors.
1987 Dec 1
Attenuation of the morphine withdrawal syndrome by inhibition of catabolism of endogenous enkephalins in the periaqueductal gray matter.
1992 Apr
Role of neutral endopeptidase in exercise-induced bronchoconstriction in asthmatic subjects.
1996 Aug
The effect of inhaled thiorphan on allergen-induced airway responses in asthmatic subjects.
1996 May
Inhibition of opioid-degrading enzymes potentiates delta9-tetrahydrocannabinol-induced antinociception in mice.
1998
Ecadotril. (S)-acetorphan, sinorphan.
1999 Apr
Perceived benefit after participating in positive or negative/neutral heart failure trials: the patients' perspective.
2001 Mar
Strategies for access to enantiomerically pure ecadotril, dexecadotril and fasidotril: a review.
2002 Jun
Effects of chronic neutral endopeptidase inhibition on the progression of left ventricular dysfunction and remodeling in dogs with moderate heart failure.
2002 May
The effect of acute angiotensin-converting enzyme and neutral endopeptidase 24.11 inhibition on plasma extravasation in the rat.
2004 Jun
Mechanism of vasopeptidase inhibitor-induced plasma extravasation: comparison of omapatrilat and the novel neutral endopeptidase 24.11/angiotensin-converting enzyme inhibitor GW796406.
2005 Dec
Neutral endopeptidase (EC 3.4.24.11) in cirrhotic liver: a new target to treat portal hypertension?
2005 Nov
Thiorphan, a neutral endopeptidase inhibitor used for diarrhoea, is neuroprotective in newborn mice.
2006 Dec
Neprilysin participates in skeletal muscle regeneration and is accumulated in abnormal muscle fibres of inclusion body myositis.
2006 Feb
Synergy between natriuretic peptides and phosphodiesterase 5 inhibitors ameliorates pulmonary arterial hypertension.
2008 Oct 15
Role of mu- and delta-opioid receptors in the nucleus accumbens in cocaine-seeking behavior.
2009 Jul
A comprehensive review of the pharmacodynamics, pharmacokinetics, and clinical effects of the neutral endopeptidase inhibitor racecadotril.
2012
Patents

Sample Use Guides

Mice: 300 mg/kg
Route of Administration: Intraperitoneal
In saturation binding studies in various mouse tissues [3H]-thiorphan exhibited an affinity (Kd value) of 0.46–0.77 nM, and the density of [3H]-thiorphan binding sites was well correlated with measured enkephalinase activity in a panel of 11 different mouse tissues.
Name Type Language
Thiorphan, (S)-
Common Name English
(+)-Thiorphan
Common Name English
Glycine, N-[(2S)-2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-
Systematic Name English
N-[(2S)-2-(Mercaptomethyl)-1-oxo-3-phenylpropyl]glycine
Systematic Name English
LY-171436
Code English
Thiorphan, (+)-
Common Name English
(S)-Thiorphan
Common Name English
LY171436
Code English
Code System Code Type Description
FDA UNII
XJ8Z52GK3X
Created by admin on Sat Dec 16 20:01:49 GMT 2023 , Edited by admin on Sat Dec 16 20:01:49 GMT 2023
PRIMARY
CAS
95909-00-5
Created by admin on Sat Dec 16 20:01:49 GMT 2023 , Edited by admin on Sat Dec 16 20:01:49 GMT 2023
PRIMARY
PUBCHEM
4369380
Created by admin on Sat Dec 16 20:01:49 GMT 2023 , Edited by admin on Sat Dec 16 20:01:49 GMT 2023
PRIMARY