DT-Web

DB00659 - Acamprosate


Identification
Name Acamprosate
Accession Number DB00659 (APRD00661)
Type small molecule
Description Acamprosate, also known by the brand name Campral™, is a drug used for treating alcohol dependence. Acamprosate is thought to stabilize the chemical balance in the brain that would otherwise be disrupted by alcoholism, possibly by blocking glutaminergic N-methyl-D-aspartate receptors, while gamma-aminobutyric acid type A receptors are activated. Reports indicate that acamprosate only works with a combination of attending support groups and abstinence from alcohol. Certain serious side effects include allergic reactions, irregular heartbeats, and low or high blood pressure, while less serious side effects include headaches, insomnia, and impotence. Acamprosate should not be taken by people with kidney problems or allergies to the drug.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 181.21
Groups approved
Monoisotopic Weight 181.040878535
Pharmacology
Indication For the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation
Mechanism of action 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.
Absorption The absolute bioavailability of acamprosate after oral administration is about 11%. The food effect on absorption is not clinically significant and no adjustment of dose is necessary.
Protein binding Non detectable
Biotransformation Acamprosate does not undergo metabolism.
Route of elimination Following oral administration of CAMPRAL(R), the major route of excretion is via the kidneys as acamprosate.
Toxicity In all reported cases of acute overdosage with acamprosate (total reported doses of up to 56 grams of acamprosate calcium), the only symptom that could be reasonably associated with acamprosate was diarrhea.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
  • Taking the product with food reduces its Cmax by 42% and total drug exposure by 23% (not considered significant).

Targets


Glutamate [NMDA] receptor subunit 3A
Name Glutamate [NMDA] receptor subunit 3A
Gene Name GRIN3A
Pharmacological action yes
Actions antagonist
References
  • Smothers CT, Woodward JJ: Pharmacological characterization of glycine-activated currents in HEK 293 cells expressing N-methyl-D-aspartate NR1 and NR3 subunits. J Pharmacol Exp Ther. 2007 Aug;322(2):739-48. Epub 2007 May 14. - Pubmed
DTHybrid score 0.5359
Metabotropic glutamate receptor 5
Name Metabotropic glutamate receptor 5
Gene Name GRM5
Pharmacological action yes
Actions antagonist
References
  • De Witte P, Littleton J, Parot P, Koob G: Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action. CNS Drugs. 2005;19(6):517-37. - Pubmed
DTHybrid score 0.814
Metabotropic glutamate receptor 1
Name Metabotropic glutamate receptor 1
Gene Name GRM1
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.1263
Metabotropic glutamate receptor 2
Name Metabotropic glutamate receptor 2
Gene Name GRM2
Pharmacological action unknown
Actions antagonist
References
  • Heilig M, Egli M: Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76. Epub 2006 Mar 20. - Pubmed
DTHybrid score 0.907
Metabotropic glutamate receptor 3
Name Metabotropic glutamate receptor 3
Gene Name GRM3
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 0.9069

Transporters


Proton-coupled amino acid transporter 1
Name Proton-coupled amino acid transporter 1
Gene Name SLC36A1
Actions Not Available
References
  • Thwaites DT, Basterfield L, McCleave PM, Carter SM, Simmons NL: Gamma-Aminobutyric acid (GABA) transport across human intestinal epithelial (Caco-2) cell monolayers. Br J Pharmacol. 2000 Feb;129(3):457-64. - Pubmed
DTHybrid score 1.2497

Predictions


Id Partner name Gene Name Score
1995 Sodium channel protein type 9 subunit alpha SCN9A 0.0841
280 4-aminobutyrate aminotransferase, mitochondrial ABAT 0.0739
240 Gamma-aminobutyric acid type B receptor, subunit 1 GABBR1 0.0655
4604 Liver carboxylesterase 1 CES1 0.062
6013 Cytochrome P450 2E1 CYP2E1 0.0586
4512 Cytochrome P450 3A4 CYP3A4 0.0519
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.044
587 Serum albumin ALB 0.0429
6030 Cytochrome P450 2B6 CYP2B6 0.0406
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0385
831 D(2) dopamine receptor DRD2 0.0343
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0339
174 Sigma 1-type opioid receptor SIGMAR1 0.0331
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0287
3923 Cholinesterase BCHE 0.0277
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0276
341 5-hydroxytryptamine 3 receptor HTR3A 0.027
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0269
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.0234
532 Neutral amino acid transporter A SLC1A4 0.0203
4070 Probable alanyl-tRNA synthetase, mitochondrial AARS2 0.0203
323 Alanyl-tRNA synthetase, cytoplasmic AARS 0.0203
735 Alanine aminotransferase 1 GPT 0.0197
3904 Alanine aminotransferase 2 GPT2 0.0197
114 Alanine--glyoxylate aminotransferase 2, mitochondrial AGXT2 0.0192
349 Serine--pyruvate aminotransferase AGXT 0.0186
713 Sodium-dependent dopamine transporter SLC6A3 0.0184
6016 Cytochrome P450 2C19 CYP2C19 0.0176
6151 Monocarboxylate transporter 10 SLC16A10 0.0176
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.017
3899 Alanine--glyoxylate aminotransferase 2-like 2 AGXT2L2 0.0154
435 Kynureninase KYNU 0.0151
4654 Kynureninase kynU 0.0151
169 Cysteine desulfurase, mitochondrial NFS1 0.0147
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0139
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0136
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0132
1588 Multidrug resistance protein 1 ABCB1 0.0127
4757 Cytochrome P450 2C9 CYP2C9 0.0123
694 Matrix protein 2 M 0.0121
617 Muscarinic acetylcholine receptor M2 CHRM2 0.012
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0115
482 Glycine receptor subunit alpha-1 GLRA1 0.0115
6144 Solute carrier family 22 member 2 SLC22A2 0.0113
820 Glycine receptor subunit alpha-2 GLRA2 0.0101
427 Substance-P receptor TACR1 0.0098
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0094
927 Metabotropic glutamate receptor 8 GRM8 0.0093
926 Metabotropic glutamate receptor 7 GRM7 0.0093
925 Metabotropic glutamate receptor 4 GRM4 0.0093
4016 Excitatory amino acid transporter 5 SLC1A7 0.0093
4024 Mitochondrial glutamate carrier 2 SLC25A18 0.0093
4025 Mitochondrial glutamate carrier 1 SLC25A22 0.0093
4022 Glutamate--ammonia ligase domain-containing protein 1 LGSN 0.0093
4026 Aspartyl aminopeptidase DNPEP 0.0093
4021 Probable glutamyl-tRNA synthetase, mitochondrial EARS2 0.0093
664 Glutamate decarboxylase 2 GAD2 0.0093
3890 Glutamate decarboxylase 2 GAD2 0.0093
1912 Excitatory amino acid transporter 1 SLC1A3 0.0093
924 Glutamate receptor, ionotropic kainate 3 GRIK3 0.0093
915 Delta 1-pyrroline-5-carboxylate synthetase ALDH18A1 0.0093
4019 Excitatory amino acid transporter 4 SLC1A6 0.0093
919 Glutamate receptor, ionotropic kainate 4 GRIK4 0.0093
4023 N-acetylglutamate synthase, mitochondrial NAGS 0.0093
920 Glutamate receptor, ionotropic kainate 5 GRIK5 0.0093
4018 Glutamate receptor delta-2 subunit GRID2 0.0093
4027 Glutamate receptor delta-1 subunit GRID1 0.0093
1047 Excitatory amino acid transporter 2 SLC1A2 0.0093
4020 Glutamyl aminopeptidase ENPEP 0.0093
922 Glutamate receptor 4 GRIA4 0.0093
4017 5-oxoprolinase OPLAH 0.0093
4924 Cytochrome P450 2C8 CYP2C8 0.0092
3876 Aromatic-L-amino-acid decarboxylase DDC 0.009
4119 Cytochrome P450 2D6 CYP2D6 0.0088
467 Delta-type opioid receptor OPRD1 0.0082
4058 Glycine N-acyltransferase-like protein 2 GLYATL2 0.0079
4056 N-arachidonyl glycine receptor GPR18 0.0079
4061 Peroxisomal sarcosine oxidase PIPOX 0.0079
4055 Bile acid CoA:amino acid N-acyltransferase BAAT 0.0079
1236 Sodium- and chloride-dependent glycine transporter 1 SLC6A9 0.0079
4060 Vesicular inhibitory amino acid transporter SLC32A1 0.0079
4057 Glycine N-acyltransferase GLYAT 0.0079
4059 Glycine N-acyltransferase-like protein 1 GLYATL1 0.0079
1088 5-aminolevulinate synthase, erythroid-specific, mitochondrial ALAS2 0.0079
1466 Glycyl-tRNA synthetase GARS 0.0079
4062 Sodium- and chloride-dependent glycine transporter 2 SLC6A5 0.0079
847 Mu-type opioid receptor OPRM1 0.0078
3984 Probable glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial PET112L 0.0078
5 Glutaminase liver isoform, mitochondrial GLS2 0.0078
917 Glutaminase kidney isoform, mitochondrial GLS 0.0078
355 GMP synthase [glutamine-hydrolyzing] GMPS 0.0078
4353 GMP synthase [glutamine-hydrolyzing] guaA 0.0078
3991 Glutamine-dependent NAD(+) synthetase NADSYN1 0.0078
3982 Phosphoribosylformylglycinamidine synthase PFAS 0.0078
5261 Phosphoribosylformylglycinamidine synthase purL 0.0078
824 Sodium-dependent serotonin transporter SLC6A4 0.0077
830 Glutamate dehydrogenase 2, mitochondrial GLUD2 0.0077
668 Glutamate--cysteine ligase regulatory subunit GCLM 0.0077
625 Glutamate carboxypeptidase 2 FOLH1 0.0076
665 Phosphoserine aminotransferase PSAT1 0.0073
4652 Phosphoserine aminotransferase serC 0.0073
801 Kynurenine/alpha-aminoadipate aminotransferase mitochondrial AADAT 0.0073
420 Glutamate decarboxylase 1 GAD1 0.0073
3900 Glutamate decarboxylase 1 GAD1 0.0073
3895 Kynurenine--oxoglutarate transaminase 3 CCBL2 0.0073
382 Glutamate receptor, ionotropic kainate 1 GRIK1 0.0072
5718 Cytochrome P450 2A6 CYP2A6 0.007
923 Glutamate receptor 3 GRIA3 0.0069
1671 Excitatory amino acid transporter 3 SLC1A1 0.0068
186 Glutamate--cysteine ligase catalytic subunit GCLC 0.0067
448 Vitamin K-dependent gamma-carboxylase GGCX 0.0067
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.0067
3877 Growth-inhibiting protein 18 GIG18 0.0067
3939 Amine oxidase [flavin-containing] B MAOB 0.0067
319 Opioid receptor, sigma 1 OPRS1 0.0066
4054 Glycine cleavage system H protein, mitochondrial GCSH 0.0066
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0066
83 Alpha-aminoadipic semialdehyde synthase, mitochondrial AASS 0.0066
914 Formimidoyltransferase-cyclodeaminase FTCD 0.0065
426 Aspartate aminotransferase, mitochondrial GOT2 0.0064
210 Bifunctional aminoacyl-tRNA synthetase [Includes: Glutamyl-tRNA synthetase EPRS 0.0064
763 Tyrosine aminotransferase TAT 0.0064
5493 Tyrosine aminotransferase Not Available 0.0064
586 Aspartate aminotransferase, cytoplasmic GOT1 0.0061
62 Glycine receptor subunit beta GLRB 0.0061
575 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial GCAT 0.0061
455 5-aminolevulinate synthase, nonspecific, mitochondrial ALAS1 0.0061
681 Glycine dehydrogenase [decarboxylating], mitochondrial GLDC 0.0061
242 Asparagine synthetase [glutamine-hydrolyzing] ASNS 0.0061
383 Glycine amidinotransferase, mitochondrial GATM 0.006
411 Glycine N-methyltransferase GNMT 0.0059
795 Branched-chain-amino-acid aminotransferase, mitochondrial BCAT2 0.0059
6145 Solute carrier family 22 member 1 SLC22A1 0.0057
207 Glutathione synthetase GSS 0.0057
5269 Glutathione synthetase gshB 0.0057
574 Branched-chain-amino-acid aminotransferase, cytosolic BCAT1 0.0057
33 Cystine/glutamate transporter SLC7A11 0.0056
705 Glutamate receptor 1 GRIA1 0.0056
3426 Glutamine synthetase glnA 0.0056
3987 Glutamine synthetase GLUL 0.0056
3884 SHMT2 protein SHMT2 0.0055
3901 SHMT2 protein SHMT2 0.0055
3885 Hypothetical protein DKFZp686P09201 DKFZp686P09201 0.0055
3879 Serine hydroxymethyltransferase 2 Not Available 0.0055
321 Serine hydroxymethyltransferase, mitochondrial SHMT2 0.0055
251 Alcohol dehydrogenase 1A ADH1A 0.0054
6107 Cytochrome P450 3A7 CYP3A7 0.0053
367 Serine hydroxymethyltransferase, cytosolic SHMT1 0.005
4118 Cytochrome P450 3A5 CYP3A5 0.005
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.005
461 Glycine receptor subunit alpha-3 GLRA3 0.005
20 Prostaglandin G/H synthase 1 PTGS1 0.0048
444 Alcohol dehydrogenase 1B ADH1B 0.0047
4200 Cytochrome P450 1A2 CYP1A2 0.0047
696 Kappa-type opioid receptor OPRK1 0.0046
738 Monocarboxylate transporter 1 SLC16A1 0.0046
492 Histamine H1 receptor HRH1 0.0046
468 Cytochrome P450 4A11 CYP4A11 0.0045
590 5-hydroxytryptamine 2C receptor HTR2C 0.0044
1768 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 subunit GNG2 0.0043
1571 G protein-activated inward rectifier potassium channel 1 KCNJ3 0.0043
1268 Neuropeptide S receptor NPSR1 0.0043
1581 G protein-activated inward rectifier potassium channel 2 KCNJ6 0.0043
918 Glutamate receptor, ionotropic kainate 2 GRIK2 0.0043
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0041
517 Alcohol dehydrogenase 1C ADH1C 0.0041
921 Glutamate receptor 2 GRIA2 0.004
6073 Potassium channel subfamily K member 9 KCNK9 0.0039
6072 Potassium channel subfamily K member 3 KCNK3 0.0039
6106 Cytochrome P450 2C18 CYP2C18 0.0035
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0034
3811 Cytochrome P450 19A1 CYP19A1 0.0033
241 Calcium-transporting ATPase type 2C member 1 ATP2C1 0.0031
537 ATP synthase delta chain, mitochondrial ATP5D 0.003
6024 Cytochrome P450 1A1 CYP1A1 0.0029
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0028
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0028
2207 Rhodopsin RHO 0.0028
↑