Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C27H30N2O2 |
Molecular Weight | 414.5393 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN([C@H](CN1CC[C@H](O)C1)C2=CC=CC=C2)C(=O)C(C3=CC=CC=C3)C4=CC=CC=C4
InChI
InChIKey=JHLHNYVMZCADTC-LOSJGSFVSA-N
InChI=1S/C27H30N2O2/c1-28(25(21-11-5-2-6-12-21)20-29-18-17-24(30)19-29)27(31)26(22-13-7-3-8-14-22)23-15-9-4-10-16-23/h2-16,24-26,30H,17-20H2,1H3/t24-,25+/m0/s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/22346361Curator's Comment: description was created based on several sources, including:
http://www.tiogapharma.com/Drug-Development/index.html
https://www.ncbi.nlm.nih.gov/pubmed/20809870
https://www.wikigenes.org/e/chem/e/179340.html
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22346361
Curator's Comment: description was created based on several sources, including:
http://www.tiogapharma.com/Drug-Development/index.html
https://www.ncbi.nlm.nih.gov/pubmed/20809870
https://www.wikigenes.org/e/chem/e/179340.html
Asimadoline is an orally active, highly selective kappa-opioid receptor agonist with approximately 500-fold greater affinity for human kappa-, as compared with either delta- or mu-opioid receptors. Due to its high selectivity for the kappa-opioid receptor, asimadoline does not produce mu-opioid like side effects. It is investigated for use/treatment in irritable bowel syndrome, pruritus, postoperative ileus. A drug interaction study investigating the coadministration of asimadoline with ketoconazole was performed in healthy volunteers - a two to three-fold increase in AUC and Cmax of asimadoline was observed with concomitant administration of ketoconazole. The most common adverse events are diarrhea, nausea, sinusitis, headache and fatigue.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10369454
Curator's Comment: Asimadoline has only a limited ability to penetrate the blood-brain barrier.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL237 |
1.2 nM [IC50] | ||
Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22346361 |
601.0 nM [IC50] | ||
Target ID: CHEMBL236 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22346361 |
597.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
213.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ASIMADOLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
90.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ASIMADOLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
18 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
ASIMADOLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1205.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ASIMADOLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
375.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ASIMADOLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
58.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
ASIMADOLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10.57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ASIMADOLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
15.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
ASIMADOLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
2.55 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
ASIMADOLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
ASIMADOLINE serum | Homo sapiens |
Doses
Dose | Population | Adverse events |
---|---|---|
0.15 mg 2 times / day multiple, oral (unknown) Dose: 0.15 mg, 2 times / day Route: oral Route: multiple Dose: 0.15 mg, 2 times / day Sources: |
unhealthy, ADULT n = 146 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 146 Sources: |
Disc. AE: Diarrhoea, Diarrhoea... AEs leading to discontinuation/dose reduction: Diarrhoea (3.4%) Sources: Diarrhoea (3.4%) |
0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: |
unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: |
Disc. AE: vomiting, nausea... AEs leading to discontinuation/dose reduction: vomiting (2.6%) Sources: nausea (2.6%) vomiting (2.6%) nausea (2.6%) |
1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: |
unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: |
Disc. AE: diarrhoea, diarrhoea... AEs leading to discontinuation/dose reduction: diarrhoea (2.1%) Sources: diarrhoea (2.1%) abdominal pain (2.1%) abdominal pain (2.1%) vomiting (0.7%) vomiting (0.7%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Diarrhoea | 3.4% Disc. AE |
0.15 mg 2 times / day multiple, oral (unknown) Dose: 0.15 mg, 2 times / day Route: oral Route: multiple Dose: 0.15 mg, 2 times / day Sources: |
unhealthy, ADULT n = 146 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 146 Sources: |
Diarrhoea | 3.4% Disc. AE |
0.15 mg 2 times / day multiple, oral (unknown) Dose: 0.15 mg, 2 times / day Route: oral Route: multiple Dose: 0.15 mg, 2 times / day Sources: |
unhealthy, ADULT n = 146 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 146 Sources: |
nausea | 2.6% Disc. AE |
0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: |
unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: |
nausea | 2.6% Disc. AE |
0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: |
unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: |
vomiting | 2.6% Disc. AE |
0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: |
unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: |
vomiting | 2.6% Disc. AE |
0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: |
unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: |
vomiting | 0.7% Disc. AE |
1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: |
unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: |
vomiting | 0.7% Disc. AE |
1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: |
unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: |
abdominal pain | 2.1% Disc. AE |
1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: |
unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: |
abdominal pain | 2.1% Disc. AE |
1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: |
unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: |
diarrhoea | 2.1% Disc. AE |
1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: |
unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: |
diarrhoea | 2.1% Disc. AE |
1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: |
unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
The kappa-opioid agonist, asimadoline, alters cytokine gene expression in adjuvant arthritis. | 2001 Sep |
|
CJ-15,208, a novel kappa opioid receptor antagonist from a fungus, Ctenomyces serratus ATCC15502. | 2002 Oct |
|
Effects of a kappa-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans. | 2003 Apr |
|
Gateways to clinical trials. | 2003 Jul-Aug |
|
Gateways to clinical trials. | 2003 Jun |
|
Effects of asimadoline, a kappa-opioid agonist, on satiation and postprandial symptoms in health. | 2003 Sep 1 |
|
Functional dyspepsia: drugs for new (and old) therapeutic targets. | 2004 Aug |
|
Effect of asimadoline, a kappa opioid agonist, on pain induced by colonic distension in patients with irritable bowel syndrome. | 2004 Jul 15 |
|
Gateways to clinical trials. | 2004 Mar |
|
Gateways to clinical trials. | 2004 Nov |
|
The kappa-opioid receptor agonist asimadoline inhibits epithelial transport in mouse trachea and colon. | 2004 Oct 25 |
|
Peripheral opioids for functional GI disease: a reappraisal. | 2006 |
|
Ligands regulate cell surface level of the human kappa opioid receptor by activation-induced down-regulation and pharmacological chaperone-mediated enhancement: differential effects of nonpeptide and peptide agonists. | 2006 Nov |
|
Gateways to clinical trials. | 2007 Nov |
|
Subcutaneous, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia in the rat. | 2007 Nov 14 |
|
Opioid-induced bowel dysfunction. | 2008 Feb |
|
Asimadoline, a kappa-opioid agonist, and satiation in functional dyspepsia. | 2008 Jun 1 |
|
Novel pharmacology: asimadoline, a kappa-opioid agonist, and visceral sensation. | 2008 Sep |
|
SA14867, a newly synthesized kappa-opioid receptor agonist with antinociceptive and antipruritic effects. | 2010 Nov 25 |
|
Asimadoline in the treatment of irritable bowel syndrome. | 2010 Oct |
Patents
Sample Use Guides
0.5 mg and placebo were administered twice daily for up to 12 weeks.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10369454
The cell lines (LLC-PK1, L-mdr1a, L-mdr1b and L-MDR1) were grown to confluent polarized monolayers on porous membrane filters, and polarized trans-epithelial transport of [14C]-asimadoline (10 μm) was determined. Asimadoline is well transported in vitro by mouse mdr1a P-gp and also by human MDR1 P-gp but not efficiently by mouse mdr1b P-gp.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C241
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CHEMBL1190199
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ASIMADOLINE
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7459
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SUB05581MIG
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DTXSID60165285
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m2093
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D0VK52NV5M
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C72137
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100000086607
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DB05104
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C092095
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179340
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153205-46-0
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)