 Chemical Structure.png)
Acamprosate calcium (also known as Campral EC), a medication used in the treatment of alcohol dependence, is a GABA receptor agonist and modulator of glutamatergic systems; it reduces alcohol consumption in animal models of alcohol addiction. Acamprosate is thought to stabilize the chemical balance in the brain that would otherwise be disrupted by alcohol withdrawal. Reports indicate that acamprosate works to best advantage in combination with psychosocial support and can help facilitate reduced consumption as well as full abstinence. Until it became a generic in the United States, Campral was manufactured and marketed in the United States by Forest Laboratories, while Merck KGaA markets it outside the US.
Physicochemical Properties
| Molecular Formula | C10H20CAN2O8S2 | |
| Molecular Weight | 400.47 | |
| Exact Mass | 400.028 | |
| CAS # | 77337-73-6 | |
| Related CAS # | Acamprosate-d3 calcium;1225580-94-8;Acamprosate;77337-76-9 | |
| PubChem CID | 155434 | |
| Appearance | White to off-white solid powder | |
| Melting Point | >300ºC | |
| LogP | 1.059 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 8 | |
| Rotatable Bond Count | 6 | |
| Heavy Atom Count | 23 | |
| Complexity | 202 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | BUVGWDNTAWHSKI-UHFFFAOYSA-L | |
| InChi Code | InChI=1S/2C5H11NO4S.Ca/c2*1-5(7)6-3-2-4-11(8,9)10;/h2*2-4H2,1H3,(H,6,7)(H,8,9,10);/q;;+2/p-2 | |
| Chemical Name | Calcium 3-(acetylamino)propane-1-sulfonate | |
| Synonyms |
|
|
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
|
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
Acamprosate acts as a partial coagonist/modulator of NMDA receptors, depending on concentration and receptor activity. It may also interact with GABA receptors, though recent studies indicate little direct effect on GABAA or glycine receptors. The drug modulates NMDA receptor subunit expression and regulates glutamatergic neurotransmission, helping to balance excitatory and inhibitory neurotransmitter systems disrupted by chronic alcohol use.[2] |
| ln Vitro |
In vitro activity: Acamprosate has low bioavailability, but also has an excellent tolerability and safety profile. In comparison with naltrexone and disulfiram, which are the other FDA-approved treatments for alcohol dependence, acamprosate is unique in that it is not metabolized by the liver and is also not impacted by alcohol use, so can be administered to patients with hepatitis or liver disease (a common comorbid condition among individuals with alcohol dependence) and to patients who continue drinking alcohol. Acamprosate shows biphasic effects on NMDA receptors in isolated neonatal rat respiratory networks, enhancing low receptor activity at low concentrations and inhibiting highly activated receptors at high concentrations.[2] In Xenopus oocytes expressing neuronal receptors and ion channels, acamprosate modulates receptor activity, particularly affecting NMDA receptor function.[2] Studies using rat brain tissue identified a spermidine-sensitive binding site for acamprosate, suggesting a specific mechanism of action at NMDA receptors.[2] |
| ln Vivo |
Acamprosate calcium(Campral EC) is a GABA receptor agonist and modulator of glutamatergic systems; reduces alcohol consumption in animal models of alcohol addiction. In alcohol-dependent patients, acamprosate significantly reduces the risk of returning to any drinking by 86% and increases cumulative abstinence duration by 11% compared to placebo, based on meta-analysis of 24 randomized controlled trials.[2] Acamprosate does not show superior efficacy over placebo in reducing heavy drinking days.[2] The drug also demonstrates sustained effects post-treatment, with a 9% lower risk of relapse and 9% higher abstinence duration compared to placebo after discontinuation.[2] |
| Enzyme Assay |
Acamprosate was studied for its binding to NMDA receptors using rat brain synaptosomal preparations. Binding assays characterized a spermidine-sensitive site, indicating modulation rather than direct antagonism.[2] Receptor activity modulation was assessed using Xenopus oocytes expressing NMDA and GABA receptors, showing concentration-dependent effects on ion channel currents.[2] |
| Cell Assay |
In vitro studies using Caco-2 cell monolayers evaluated intestinal absorption of acamprosate, showing low permeability and paracellular absorption.[2] Studies on chronically alcohol-exposed rat synaptosomes showed that acamprosate modulates GABA transmission, though recent evidence suggests minimal direct GABA receptor involvement.[2] |
| Animal Protocol |
N/AN/A Wild-type and ENT1 null mice (8–16 weeks old, male) were used. Chronic ethanol was administered via inhalation in a vapor chamber for 16 hours/day for 3 consecutive days, with an 8-hour withdrawal period between sessions. Prior to vapor exposure, mice received a single intraperitoneal (i.p.) injection of 1.5 g/kg ethanol (20% v/v in saline) and 68.1 mg/kg pyrazole to initiate and maintain intoxication. Blood ethanol concentrations were maintained around 150 mg/dL.[5] For acamprosate treatment, after an 8-hour withdrawal period following the last ethanol exposure, mice received acamprosate at 400 mg/kg/day (i.p.), administered as two injections of 200 mg/kg each, 12 hours apart, for 5 consecutive days. Control mice received saline at equivalent volumes.[5] In vivo 16.4T proton magnetic resonance spectroscopy ([1H] MRS) was performed to measure metabolite levels in the mPFC and NAc at baseline, after withdrawal, and after acamprosate treatment. An 8 µL volume of interest was placed in each region, and spectra were acquired using a PRESS sequence (TR=1768 ms, TE=10 ms, NA=3072). Metabolites were quantified using LCModel software relative to creatine as an internal standard.[5] |
| ADME/Pharmacokinetics |
Acamprosate has low oral bioavailability (approximately 11%). It is absorbed via paracellular routes, with peak plasma concentrations occurring 4.3–15.3 hours after acute dosing, decreasing to 3.5–9.5 hours at steady state.[2] Steady state is reached within 5–7 days of dosing.[2] The drug is not metabolized by the liver and has no known active metabolites. It is primarily excreted unchanged in feces, with renal excretion correlating with bioavailability.[2] Food intake further reduces absorption.[2] Drug interaction studies show no significant interactions with naltrexone, disulfiram, diazepam, or alcohol.[2] |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the clinical use of acamprosate during breastfeeding. Based on its chemical properties it is likely to enter milk. However, the oral bioavailability of acamprosate is only 11%, so systemic effects in the breastfed infant are unlikely. If acamprosate is required by the mother, it is not a reason to discontinue breastfeeding. Monitor the breastfed infant for diarrhea. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Acamprosate is generally well-tolerated with an excellent safety profile. The most common side effect is diarrhea (16% vs. 10% in placebo).[2] Other reported side effects include abdominal pain, constipation, nausea, vomiting, gastrointestinal symptoms, and pruritus, though these are less frequent.[2] Dropout rates due to side effects are slightly higher in acamprosate groups (7–8%) compared to placebo (6–7%), but not statistically significant.[2] Serious adverse events are rare and not significantly different from placebo.[2] The drug is contraindicated in severe renal impairment due to renal excretion.[2] |
| References |
[1]. Preuss UW. Commentary on the study: impact of depressive symptoms on future alcohol use in patients with co-occurring bipolar disorder and alcohol dependence: a prospective analysis in an 8-week randomized controlled trial of acamprosate (Prisciandaro e. [2]. Witkiewitz K, Saville K, Hamreus K. Acamprosate for treatment of alcohol dependence: mechanisms, efficacy, and clinical utility. Ther Clin Risk Manag. 2012;8:45-53. [3]. Relapse prevention in alcohol dependence: acamprosate and naltrexone as a combined pharmacological strategy.Nervenarzt. 2012 Aug 15. [4]. Palucha-Poniewiera A, Pilc A. Involvement of mGlu5 and NMDA receptors in the antidepressant-like effect of acamprosate in the tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Oct 1;39(1):102-6. [5]. Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1. Neuropharmacology. 2012 Jun;62(8):2480-8. |
| Additional Infomation |
Acamprosate calcium is an organic calcium salt. It contains an acamprosate(1-). Structural analog of taurine that is used for the prevention of relapse in individuals with ALCOHOLISM. See also: Acamprosate (has active moiety). Acamprosate is FDA-approved for alcohol dependence treatment. It is unique among approved medications for not being metabolized by the liver and being safe in patients with liver disease or ongoing alcohol use.[2] It does not show abuse potential and has minimal drug interactions.[2] Efficacy is moderate compared to placebo and not consistently superior to naltrexone or disulfiram.[2] Compliance is crucial; patients taking ≥80% of prescribed doses show better outcomes.[2] Genetic factors (e.g., GABRA6, DRD2, GATA4 polymorphisms) may influence treatment response.[2] The drug may reduce alcohol cue-induced craving and stabilize HPA axis function.[2] |
Solubility Data
| Solubility (In Vitro) |
|
|||
| Solubility (In Vivo) |
|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4971 mL | 12.4853 mL | 24.9707 mL | |
| 5 mM | 0.4994 mL | 2.4971 mL | 4.9941 mL | |
| 10 mM | 0.2497 mL | 1.2485 mL | 2.4971 mL |