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targets (3)
for drugs
Identification
Name Alvimopan
Accession Number DB06274
Type small molecule
Groups approved
Description

Alvimopan is a peripherally selective opioid antagonist being investigated for the treatment of various gastrointestinal diseases and disorders.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • ADL 8-2698
Synonyms
ADL 8-2698
Salts Not Available
Brand names
Name Company
Entereg
Brand mixtures Not Available
Categories
  • Opiate Antagonists
CAS number 156053-89-3
Weight Average: 424.5326
Monoisotopic: 424.236207522
Chemical Formula C25H32N2O4
InChI Key InChIKey=UPNUIXSCZBYVBB-JVFUWBCBSA-N
InChI
InChI=1S/C25H32N2O4/c1-18-16-27(12-11-25(18,2)21-9-6-10-22(28)14-21)17-20(24(31)26-15-23(29)30)13-19-7-4-3-5-8-19/h3-10,14,18,20,28H,11-13,15-17H2,1-2H3,(H,26,31)(H,29,30)/t18-,20-,25+/m0/s1
Plain Text
IUPAC Name
2-[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanamido]acetic acid
SMILES
C[C@H]1CN(C[C@H](CC2=CC=CC=C2)C(=O)NCC(O)=O)CC[C@@]1(C)C1=CC(O)=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpiperidines
  • Amino Acids
Substructures
  • Hydroxy Compounds
  • Acetates
  • Phenols and Derivatives
  • Amino Ketones
  • Benzene and Derivatives
  • Phenylpiperidines
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Amino Acids
  • Phenyl Esters
  • Piperidines
Pharmacology
Indication Used to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis. Also investigated for use in the treatment of pain (acute or chronic).
Pharmacodynamics Not Available
Mechanism of action Alvimopan competitively binds to mu-opioid receptor in the gastrointestinal tract. Unlike methylnaltrexone (another peripherally acting mu-receptor antagonist) that bears a quaternary amine, alvimopan owes its selectivity for peripheral receptors to its kinetics. Alvimopan binds to peripheral mu-receptors with a Ki of 0.2 ng/mL and dissociates slower than most other ligands.
Absorption Alvimopan's high affinity for the peripheral mu-receptor results in an absolute oral bioavailability of less than 7%.
Volume of distribution
  • 30±10 L
Protein binding 80% to 90% of systemically available alvimopan is bound to plasma protein.
Metabolism Alvimopan undergoes no significant hepatic metabolism, but is metabolized by intestinal flora. Gut metabolism produces an active metabolite with no clinically significant contribution to drug effect.
Route of elimination Biliary secretion was considered the primary pathway for alvimopan elimination. Unabsorbed drug and unchanged alvimopan resulting from biliary excretion were then hydrolyzed to its ‘metabolite’ by gut microflora.
Half life 10 to 17 hours (gut metabolite: 10 to 18 hours)
Clearance
  • 402 +/- 89 mL/min
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Adolor corp
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Entereg 12 mg capsule 79.5 USD capsule
Patents
Country Patent Number Approved Expires (estimated)
United States 6469030 2000-11-29 2020-11-29
United States 5250542 1994-03-29 2011-03-29
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility <0.1 mg/mL [FDA] PhysProp
Predicted Properties
Property Value Source
water solubility 8.34e-03 g/l ALOGPS
logP 3.25 ALOGPS
logP 0.82 ChemAxon Molconvert
logS -4.7 ALOGPS
pKa 9.75 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 89.87 ChemAxon Molconvert
rotatable bond count 8 ChemAxon Molconvert
refractivity 120.56 ChemAxon Molconvert
polarizability 46.77 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Buchler MW, Seiler CM, Monson JR, Flamant Y, Thompson-Fawcett MW, Byrne MM, Mortensen ER, Altman JF, Williamson R: Clinical trial: alvimopan for the management of postoperative ileus after abdominal surgery: results of an international randomised, double-blind, multicentre, placebo-controlled clinical study. Aliment Pharmacol Ther. 2008 Mar 28. Pubmed
External Links
Resource Link
PubChem Compound 5488548 Link_out
PubChem Substance 99443242 Link_out
ChemSpider 4589864 Link_out
Therapeutic Targets Database DAP001140 Link_out
Drugs.com http://www.drugs.com/cdi/alvimopan.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Alvimopan Link_out
ATC Codes
  • A06AH02
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (149 KB)
MSDS show (127 KB)
Interactions
Drug Interactions
Drug Interaction
Buprenorphine Opioids like buprenorphine may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Consider therapy modification.
Butorphanol Opioid analgesics such as butorphanol may enhance the adverse/toxic effect of alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. According to alvimopan prescribing information, alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Monitor for increased alvimopan adverse effects in patients using opioids prior to alvimopan.
Food Interactions Not Available
Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: antagonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out
Gene: OPRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kraft MD: Emerging pharmacologic options for treating postoperative ileus. Am J Health Syst Pharm. 2007 Oct 15;64(20 Suppl 13):S13-20. Pubmed
  2. Buchler MW, Seiler CM, Monson JR, Flamant Y, Thompson-Fawcett MW, Byrne MM, Mortensen ER, Altman JF, Williamson R: Clinical trial: alvimopan for the management of postoperative ileus after abdominal surgery: results of an international randomised, double-blind, multicentre, placebo-controlled clinical study. Aliment Pharmacol Ther. 2008 Mar 28. Pubmed
  3. Saufl NM, Strzyzewski N: Nurses are everywhere: a practical perspective on the surgical team in managing postoperative ileus. J Perianesth Nurs. 2006 Apr;21(2A Suppl):S24-9. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  5. Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. Pubmed
  6. Schmidt WK: Alvimopan* (ADL 8-2698) is a novel peripheral opioid antagonist. Am J Surg. 2001 Nov;182(5A Suppl):27S-38S. Pubmed

2. Kappa-type opioid receptor

Pharmacological action: unknown
Actions: antagonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions

Organism class: human
UniProt ID: P41145 Link_out
Gene: OPRK1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Beattie DT, Cheruvu M, Mai N, O’Keefe M, Johnson-Rabidoux S, Peterson C, Kaufman E, Vickery R: The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone. Naunyn Schmiedebergs Arch Pharmacol. 2007 May;375(3):205-20. Epub 2007 Mar 6. Pubmed
  2. Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. Pubmed

3. Delta-type opioid receptor

Pharmacological action: unknown
Actions: antagonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins

Organism class: human
UniProt ID: P41143 Link_out
Gene: OPRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. Pubmed
  2. Beattie DT, Cheruvu M, Mai N, O’Keefe M, Johnson-Rabidoux S, Peterson C, Kaufman E, Vickery R: The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone. Naunyn Schmiedebergs Arch Pharmacol. 2007 May;375(3):205-20. Epub 2007 Mar 6. Pubmed
Comments
Drug created on March 19, 2008 10:20 / Updated on February 14, 2012 12:16