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
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
Molecular Formula | C12H15NO3S |
Molecular Weight | 253.317 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22661949https://www.ncbi.nlm.nih.gov/pubmed/3479550
Curator's Comment: Ecadotril ((S)-acetorphan) is CNS active in animals when administered parenterally. No human data available.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7001254http://adisinsight.springer.com/drugs/800001163
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2994 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3479550 |
|||
Target ID: CHEMBL2642 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3479550 |
|||
Target ID: CHEMBL2642 |
3.5 nM [Ki] | ||
Target ID: CHEMBL2994 |
140.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22661949 |
Primary | Unknown Approved UseUnknown |
||
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8872633 |
Palliative | Unknown Approved UseUnknown |
||
Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse 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%) Sources: Page: p.1142Dizziness (grade 1-2, 35%) Insomnia (6%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
inconclusive [Activation 11.2202 uM] | ||||
no | ||||
no | ||||
yes [IC50 0.1259 uM] | ||||
yes [IC50 0.3162 uM] | ||||
yes [IC50 0.6918 uM] | ||||
yes [IC50 1.2302 uM] | ||||
yes [IC50 2.512 uM] |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice. | 1980 Nov 20 |
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Thiorphan potentiation of stress-induced analgesia in the mouse. | 1982 Sep 20-27 |
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Complete differentiation between enkephalinase and angiotensin-converting enzyme inhibition by retro-thiorphan. | 1983 Jun |
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Pharmacological properties of acetorphan, a parenterally active "enkephalinase" inhibitor. | 1986 Jun |
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Naloxone-reversible antidiarrheal effects of enkephalinase inhibitors. | 1987 Dec 1 |
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Attenuation of the morphine withdrawal syndrome by inhibition of catabolism of endogenous enkephalins in the periaqueductal gray matter. | 1992 Apr |
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Role of neutral endopeptidase in exercise-induced bronchoconstriction in asthmatic subjects. | 1996 Aug |
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The effect of inhaled thiorphan on allergen-induced airway responses in asthmatic subjects. | 1996 May |
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Inhibition of opioid-degrading enzymes potentiates delta9-tetrahydrocannabinol-induced antinociception in mice. | 1998 |
|
Ecadotril. (S)-acetorphan, sinorphan. | 1999 Apr |
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Perceived benefit after participating in positive or negative/neutral heart failure trials: the patients' perspective. | 2001 Mar |
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The effect of acute angiotensin-converting enzyme and neutral endopeptidase 24.11 inhibition on plasma extravasation in the rat. | 2004 Jun |
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Mechanism of vasopeptidase inhibitor-induced plasma extravasation: comparison of omapatrilat and the novel neutral endopeptidase 24.11/angiotensin-converting enzyme inhibitor GW796406. | 2005 Dec |
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Neutral endopeptidase (EC 3.4.24.11) in cirrhotic liver: a new target to treat portal hypertension? | 2005 Nov |
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Thiorphan, a neutral endopeptidase inhibitor used for diarrhoea, is neuroprotective in newborn mice. | 2006 Dec |
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Neprilysin participates in skeletal muscle regeneration and is accumulated in abnormal muscle fibres of inclusion body myositis. | 2006 Feb |
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Synergy between natriuretic peptides and phosphodiesterase 5 inhibitors ameliorates pulmonary arterial hypertension. | 2008 Oct 15 |
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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
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6755120
Mice: 300 mg/kg
Route of Administration:
Intraperitoneal
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22661949
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.
Substance Class |
Chemical
Created
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admin
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Edited
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Record UNII |
XJ8Z52GK3X
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Record Status |
Validated (UNII)
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Record Version |
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RACEMATE -> ENANTIOMER |
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ENANTIOMER -> ENANTIOMER |
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PRODRUG -> METABOLITE ACTIVE |
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ACTIVE MOIETY |
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