Disease relevance of Campral

• Possible association of erythema multiforme with acamprosate [1].
• In contrast, renal insufficiency influences the elimination of acamprosate and it is, therefore, contraindicated under such circumstances [2].
• The pharmacokinetics of acamprosate are not modified in patients with hepatic insufficiency or chronic alcoholism [2].
• However, acamprosate prevents lapses or relapses only in a minority of patients [3].
• We compared effects of the standard 2 g dose (n=258) and an exploratory 3 g dose of acamprosate (n=83) versus placebo (n=260), and evaluated drug safety in a double-blind, placebo-controlled 6-month trial conducted in 21 outpatient clinics across the US [4].

Psychiatry related information on Campral

• Pharmacologic therapies, such as naltrexone and acamprosate, have been effective in decreasing alcohol consumption when provided along with psychosocial counseling in patients with alcohol dependence [5].
• Drawing upon data collected from 2 large samples of substance abuse treatment providers at multiple time points, this article examines the prevalence and correlates of the adoption of the currently available pharmacotherapies for alcohol dependence: disulfiram, oral naltrexone, and acamprosate [6].
• Thus, although acamprosate attenuated the expression of sensitized locomotor activity and DA release in the NAS, it did not have any consistent effect on either the intake of heroin during the maintenance phase or the relapse to heroin seeking in a drug-free state [7].
• Effects of acamprosate on conditioned negative reinforcement may be the cause of this effect, but more work is required to establish the usefulness of this model in evaluation of anti-relapse drugs [8].
• Acamprosate (calcium-acetyl homotaurinate) is a new compound used in the treatment of alcohol abuse [7].

High impact information on Campral

• Acamprosate, the Ca(2+)-salt of N-acetyl-homotaurinate, interacts with NMDA receptor-mediated glutamatergic neurotransmission in various brain regions and reduces Ca2+ fluxes through voltage-operated channels [9].
• Ethanol and amino acids in the central nervous system: assessment of the pharmacological actions of acamprosate [10].
• Naltrexone administration significantly increased plasma acetylhomotaurine (i.e., acamprosate) levels, presumably by prolonging gastric emptying [11].
• Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects [11].
• A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone [12].

Chemical compound and disease context of Campral

• However, acamprosate significantly inhibited the toxicity associated with changing medium and the toxicity induced by spermidine in these hippocampal cultures [13].
• Acamprosate is a drug used in alcoholism treatment, due to its regulating effects in glutamatergic and GABA neurotransmission, and has never been used before in the treatment of tinnitus AIM: To evaluate efficacy and safety of the acamprosate in the treatment of sensorineural tinnitus [14].

Biological context of Campral

• Clinical pharmacokinetics of acamprosate [2].
• Protein blotting demonstrated an up-regulation of NMDA-receptor subunits after acamprosate as well as after memantine or MK-801, in comparison to controls [15].
• Electrophysiology in cultured hippocampal neurons (IC(50) approx. 5.5mM) and Xenopus oocytes (NR1-1a/NR2A assemblies: IC(50) approx. 350 microM, NR1-1a/NR2B: IC(50) approx. 250 microM) consistently revealed only a weak antagonism of acamprosate on native or recombinant NMDA-receptors [15].
• Similar results were obtained when membranes were used from rats that had received 400 mg/kg/day of acamprosate in their drinking water with or without concurrent ethanol inhalation for 10 days [16].
• Acamprosate had no effect on Ca(2+)-dependent action potentials when tetrodotoxin was used to block Na+ spikes [17].

Anatomical context of Campral

• Acamprosate is absorbed via the paracellular route in the gastrointestinal tract [2].
• After acamprosate, protein levels were increased in the cortex (NR1-3/1-4: 190+/-11% of controls) and hippocampus (NR1-1/1-2: 163+/-11%) [15].
• We investigated the mechanism of action of acamprosate on a spontaneous rhythmic activity recorded from hypoglossal nerve rootlet (XII) in neonatal rat brainstem slices [18].
• Here, the pharmacological effects of acamprosate on NMDA-receptors were studied using electrophysiological techniques in different cell lines in vitro [15].
• Thus, in brain membranes from all these treatment groups, acamprosate in vitro caused inhibition of [3H]dizocilpine binding only [16].

Associations of Campral with other chemical compounds

• Biphasic effect of acamprosate on NMDA but not on GABAA receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratory network [18].
• BACKGROUND: It has been suggested that the antirelapse drug acamprosate can inhibit or potentiate glutamate/NMDA receptor-mediated responses via a polyamine site [13].
• The evidence from randomized controlled trials for the efficacy of some of the main candidates: acamprosate, naltrexone, bromocriptine, selective serotonin re-uptake inhibitors and buspirone, was examined [19].
• The effects of acamprosate on the in vivo dopamine extracellular levels in the nucleus accumbens and the involvement of N-methyl-D-aspartate (NMDA) receptors in these effects were investigated [20].
• We therefore investigated whether acamprosate normalizes HPA hyperactivity in alcoholics within the first 3 weeks of abstinence, employing a combined dexamethasone/corticotropin-releasing hormone (Dex-CRH)-test [21].

Gene context of Campral

• NMDA-receptor-mediated mechanisms may be crucial in addictive states, e.g. alcoholism, and provide a target for the novel anti-craving compound acamprosate [15].
• In HEK-293 cells, acamprosate showed almost no effect on NR1-1a/NR2A or NR1-1a/NR2B recombinants (IC(50)s not calculated) [15].
• RESULTS: CRH-stimulated cortisol secretion was significantly increased in both the acamprosate group and the group receiving no anti-relapse medication compared to a control group of 15 healthy subjects [21].
• The geometric mean of the ratio final/baseline values for serum carbohydrate-deficient transferrin was 0.802 (placebo) and 0.733 (acamprosate) (P = 0.059) [22].
• The geometric mean of the ratio final/baseline values for serum gamma-glutamyltransferase was 0.496 (placebo) and 0.415 (acamprosate) (P = 0.024) which corroborated the greater abstinence reported by the acamprosate group [22].

Analytical, diagnostic and therapeutic context of Campral

• The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period (p < 0.001, Mantel-Cox) [23].
• Acamprosate and naltrexone have each demonstrated safety and efficacy for alcohol dependence in placebo-controlled clinical trials [12].
• BACKGROUND: Acamprosate is a newly registered drug that appears to reduce alcohol-drinking in both animal models and clinical conditions [24].
• Currently, 3 US Food and Drug Administration-approved drugs are available for the treatment of alcohol dependence-disulfiram, naltrexone (oral and injectable), and acamprosate [25].
• Acamprosate suppresses the expression of morphine-induced sensitization in rats but does not affect heroin self-administration or relapse induced by heroin or stress [7].

References