ACAMPROSATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C5H11NO4S
Molecular Weight	181.21
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)NCCCS(O)(=O)=O

InChI

InChIKey=AFCGFAGUEYAMAO-UHFFFAOYSA-N

InChI=1S/C5H11NO4S/c1-5(7)6-3-2-4-11(8,9)10/h2-4H2,1H3,(H,6,7)(H,8,9,10)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/books/NBK64035/ | https://www.ncbi.nlm.nih.gov/pubmed/19412493 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021431s013lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/3398647

Acamprosate was the third medication, after disulfiram and naltrexone, to receive U.S. Food and Drug Administration (FDA) approval for postwithdrawal maintenance of alcohol abstinence. The French pharmaceutical company Laboratoires Meram began clinical development and testing of acamprosate in 1982. From 1982 to 1988, acamprosate was tested for safety and for efficacy as a treatment for alcohol dependence. Based on these studies, in 1989 Laboratoires Meram was granted marketing authorization for acamprosate in France under the trade name Aotal®. Since then, acamprosate has been extensively used and studied throughout Europe and, subsequently, in the United States. Although acamprosate has been used in Europe for more than 20 years, it was not approved by FDA until July 2004. Acamprosate became available for use in the United States in January 2005, under the trade name Campral® Delayed-Release Tablets (Merck Santé, a subsidiary of Merck KGaA, Darmstadt, Germany). Campral is currently marketed in the United States by Forest Pharmaceuticals. The mechanism of action of acamprosate in maintenance of alcohol abstinence is not completely understood. Chronic alcohol exposure is hypothesized to alter the normal balance between neuronal excitation and inhibition. in vitro and in vivo studies in animals have provided evidence to suggest acamprosate may interact with glutamate and GABA neurotransmitter systems centrally, and has led to the hypothesis that acamprosate restores this balance. It seems to inhibit NMDA receptors while activating GABA receptors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
GABA-A receptor; anion channel 202 Target ID: CHEMBL2093872 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021431s015lbl.pdf \| http://alcoholrehab.com/drug-addiction-treatment/gaba-agonist-acamprosate/ \| https://www.ncbi.nlm.nih.gov/pubmed/22346357	Positive Allosteric Modulator 179
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22346357 \| https://www.drugbank.ca/drugs/DB00659 \| https://www.ncbi.nlm.nih.gov/pubmed/11369029	Antagonist 2778	120.0 µM [Kd]
Metabotropic glutamate receptor 5 39 Target ID: CHEMBL3227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15963001 \| https://www.ncbi.nlm.nih.gov/pubmed/18540918 \| https://www.drugbank.ca/drugs/DB00659	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Alcohol addiction 21 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021431s013lbl.pdf	Primary		Approved 8429	Acamprosate Approved Use Acamprosate calcium delayed-release tablets are indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. Treatment with Acamprosate calcium delayed-release tablets should be part of a comprehensive management program that includes psychosocial support. Launch Date 2004

C_max

Value	Dose	Co-administered	Analyte	Population
244.64 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26360834	666 mg single, oral dose: 666 mg route of administration: Oral experiment type: SINGLE co-administered:		ACAMPROSATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3829.56 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26360834	666 mg single, oral dose: 666 mg route of administration: Oral experiment type: SINGLE co-administered:		ACAMPROSATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
10.26 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26360834	666 mg single, oral dose: 666 mg route of administration: Oral experiment type: SINGLE co-administered:		ACAMPROSATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf	unhealthy, adult n = 1539 Health Status: unhealthy Condition: alcohol-dependence Age Group: adult Population Size: 1539 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf	Disc. AE: Diarrhea, Nausea... AEs leading to discontinuation/dose reduction: Diarrhea (2%) Nausea (<1%) Depression (<1%) Anxiety (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf
666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93	unhealthy, adult n = 1346 Health Status: unhealthy Condition: alcohol (ethanol)-dependence Age Group: adult Population Size: 1346 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93	Disc. AE: Pain, Constipation... AEs leading to discontinuation/dose reduction: Pain (<1%) Constipation (<1%) Somnolence (<1%) Insomnia (<1%) Impotence (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93
56 g single, oral Overdose Dose: 56 g Route: oral Route: single Dose: 56 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf	unknown Health Status: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf	Other AEs: Diarrhea... Other AEs: Diarrhea Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf
66 mg 3 times / day steady, oral Dose: 66 mg, 3 times / day Route: oral Route: steady Dose: 66 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00466661	unhealthy n = 14 Health Status: unhealthy Condition: Alcohol Dependence Population Size: 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00466661	Other AEs: Anaphylactoid reaction, Diffuse pain... Other AEs: Anaphylactoid reaction (serious, 1 patient) Diffuse pain (below serious, 2 patients) Suicidal ideation (below serious, 2 patients) Tremor (below serious, 2 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00466661

AEs

AE	Significance	Dose	Population
Diarrhea	2% Disc. AE	666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf	unhealthy, adult n = 1539 Health Status: unhealthy Condition: alcohol-dependence Age Group: adult Population Size: 1539 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf
Anxiety	<1% Disc. AE	666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf	unhealthy, adult n = 1539 Health Status: unhealthy Condition: alcohol-dependence Age Group: adult Population Size: 1539 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf
Depression	<1% Disc. AE	666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf	unhealthy, adult n = 1539 Health Status: unhealthy Condition: alcohol-dependence Age Group: adult Population Size: 1539 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf
Nausea	<1% Disc. AE	666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf	unhealthy, adult n = 1539 Health Status: unhealthy Condition: alcohol-dependence Age Group: adult Population Size: 1539 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf
Constipation	<1% Disc. AE	666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93	unhealthy, adult n = 1346 Health Status: unhealthy Condition: alcohol (ethanol)-dependence Age Group: adult Population Size: 1346 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93
Impotence	<1% Disc. AE	666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93	unhealthy, adult n = 1346 Health Status: unhealthy Condition: alcohol (ethanol)-dependence Age Group: adult Population Size: 1346 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93
Insomnia	<1% Disc. AE	666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93	unhealthy, adult n = 1346 Health Status: unhealthy Condition: alcohol (ethanol)-dependence Age Group: adult Population Size: 1346 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93
Pain	<1% Disc. AE	666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93	unhealthy, adult n = 1346 Health Status: unhealthy Condition: alcohol (ethanol)-dependence Age Group: adult Population Size: 1346 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93
Somnolence	<1% Disc. AE	666 mg 3 times / day steady, oral Recommended Dose: 666 mg, 3 times / day Route: oral Route: steady Dose: 666 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93	unhealthy, adult n = 1346 Health Status: unhealthy Condition: alcohol (ethanol)-dependence Age Group: adult Population Size: 1346 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Medr_P2.pdf Page: p. 93
Diarrhea		56 g single, oral Overdose Dose: 56 g Route: oral Route: single Dose: 56 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf	unknown Health Status: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21431lbl.pdf
Diffuse pain	below serious, 2 patients	66 mg 3 times / day steady, oral Dose: 66 mg, 3 times / day Route: oral Route: steady Dose: 66 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00466661	unhealthy n = 14 Health Status: unhealthy Condition: Alcohol Dependence Population Size: 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00466661
Suicidal ideation	below serious, 2 patients	66 mg 3 times / day steady, oral Dose: 66 mg, 3 times / day Route: oral Route: steady Dose: 66 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00466661	unhealthy n = 14 Health Status: unhealthy Condition: Alcohol Dependence Population Size: 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00466661
Tremor	below serious, 2 patients	66 mg 3 times / day steady, oral Dose: 66 mg, 3 times / day Route: oral Route: steady Dose: 66 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00466661	unhealthy n = 14 Health Status: unhealthy Condition: Alcohol Dependence Population Size: 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00466661
Anaphylactoid reaction	serious, 1 patient	66 mg 3 times / day steady, oral Dose: 66 mg, 3 times / day Route: oral Route: steady Dose: 66 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00466661	unhealthy n = 14 Health Status: unhealthy Condition: Alcohol Dependence Population Size: 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00466661

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 CYP2E1 882	OAT1 326 OAT3 339	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_BioPharmr.pdf#page=30 Page: 30.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_BioPharmr.pdf#page=30 Page: 30.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_BioPharmr.pdf#page=30 Page: 30.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_BioPharmr.pdf#page=30 Page: 30.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_BioPharmr.pdf#page=30 Page: 30.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_BioPharmr.pdf#page=30 Page: 30.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_BioPharmr.pdf#page=30 Page: 30.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_BioPharmr.pdf#page=30 Page: 30.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OAT3 339	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238232/	no
OAT1 326	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238232/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral_Pharmr_P1.pdf#page=37 Page: 37.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:51041	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:51041
MolPort	MolPort-006-138-766	https://www.molport.com/shop/molecule-link/MolPort-006-138-766
ZINC	ZINC000001554588	http://zinc15.docking.org/substances/ZINC000001554588

PubMed

Title	Date	PubMed
[The neuroprotective effect of the glutamate antagonist acamprosate following experimental cerebral ischemia. A study with the lipid peroxidase inhibitor u-101033e].	2000 Sep	11076270
Effects of acamprosate and scopolamine on the working memory of rats in a three-panel runway task.	2001	11762691
Effect of acamprosate and naltrexone, alone or in combination, on ethanol consumption.	2001 Feb	11331108
Neurotoxic effect of acamprosate, n-acetyl-homotaurine, in cultured neurons.	2001 Jan-Feb	11173982
The European acamprosate trials: conclusions for research and therapy.	2001 Jan-Feb	11173981
Combined behavioral and pharmacologic treatments of alcoholism.	2001 Jul	11480392
[Therapeutic strategies and help in chronic alcoholism].	2001 Jun	11467216
Role of polyamines and NMDA receptors in ethanol dependence and withdrawal.	2001 May	11391062
Efficacy of naltrexone and acamprosate for alcoholism treatment: a meta-analysis.	2001 Sep	11584154
Acamprosate is neuroprotective against glutamate-induced excitotoxicity when enhanced by ethanol withdrawal in neocortical cultures of fetal rat brain.	2001 Sep	11584146
Naltrexone versus acamprosate: one year follow-up of alcohol dependence treatment.	2001 Sep-Oct	11524308
Opioid antagonists for alcohol dependence.	2002	12076425
[Acamprosate and psychosocial intervention. An integrative treatment approach for prevention of alcohol dependent patients in Switzerland].	2002 Apr 24	12038194
Acamprosate inhibits the binding and neurotoxic effects of trans-ACPD, suggesting a novel site of action at metabotropic glutamate receptors.	2002 Dec	12500101
Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release.	2002 Feb 15	11864639
New pharmacotherapies for alcohol dependence.	2002 Jul 15	12098353
[Long-term treatment of alcohol dependance].	2002 May	12068285
Acamprosate has no effect on NMDA-induced toxicity but reduces toxicity induced by spermidine or by changing the medium in organotypic hippocampal slice cultures from rat.	2002 May	12045473
Effects of acamprosate and some polyamine site ligands of NMDA receptor on short-term memory in rats.	2002 May 24	12191586
The European NEAT program: an integrated approach using acamprosate and psychosocial support for the prevention of relapse in alcohol-dependent patients with a statistical modeling of therapy success prediction.	2002 Oct	12394286
Acamprosate reduces context-dependent ethanol effects.	2002 Oct	12373414
The anti-craving taurine derivative acamprosate: failure to extinguish morphine conditioned place preference.	2003	12908633
Research advances in the understanding and treatment of addiction.	2003	12857662
Acamprosate.	2003	12638639
Local acamprosate modulates dopamine release in the rat nucleus accumbens through NMDA receptors: an in vivo microdialysis study.	2003 Feb	12595952
[The role of the glutamatergic system in alcohol addiction].	2003 Jul	12947541
Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects.	2003 Jun	12826990
Effects of acamprosate on excitatory amino acids during multiple ethanol withdrawal periods.	2003 Mar	12658112
[Preventing recurrence after alcohol withdrawal treatment with drugs. Reducing the drive to drink].	2003 May 8	12813988
Efficacy of acamprosate in the treatment of alcohol-dependent outpatients.	2003 Sep	12975689
Prevention of relapse to addiction: information for the practitioner.	2004 Feb	15146782
Acamprosate in alcohol dependence: a randomized controlled efficacy study in a standard clinical setting.	2004 Jan	15000513
The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis.	2004 Jan	14745302
NR2B subunit selective NMDA antagonists inhibit neurotoxic effect of alcohol-withdrawal in primary cultures of rat cortical neurones.	2004 Jan	12963084
A comparison of two intensities of psychosocial intervention for alcohol dependent patients treated with acamprosate.	2004 May-Jun	15082464
Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats.	2005 Jan	15138444

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of CAMPRAL (Acamprosate) is two 333 mg tablets (each dose should total 666 mg) taken three times daily. Although dosing may be done without regard to meals, dosing with meals was employed during clinical trials and is suggested as an aid to compliance in those patients who regularly eat three meals daily. A lower dose may be effective in some patients. Treatment with CAMPRAL should be initiated as soon as possible after the period of alcohol withdrawal, when the patient has achieved abstinence, and should be maintained if the patient relapses. CAMPRAL should be used as part of a comprehensive psychosocial treatment program.

Route of Administration: Oral

In Vitro Use Guide

Acamprosate (0.1-1 mM) added to the perfusion fluid in vitro reduced excitatory and inhibitory postsynaptic potentials and the depolarizing responses evoked by iontophoretic application of the excitatory amino acids, L-glutamate, L-aspartate, L-homocysteate and N-methyl-D-aspartate, but did not alter the responses to gamma-aminobutyric acid in rat neocortical neurons.

Name

Type

Language

ACAMPROSATE

Official Name

English

Acamprosate [WHO-DD]

Common Name

English

3-(ACETYLAMINO)PROPANE-1-SULFONATE

Systematic Name

English

acamprosate [INN]

Common Name

English

AOTAL

Brand Name

English

1-PROPANESULFONIC ACID, 3-(ACETYLAMINO)-

Common Name

English

ACAMPROSATE [VANDF]

Common Name

English

ACAMPROSATE [HSDB]

Common Name

English

3-(ACETYLAMINO)PROPANE-1-SULPHONATE

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

392413