Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Alcohol Clin Exp Res
2008 Feb 01;322:188-96. doi: 10.1111/j.1530-0277.2007.00569.x.
Show Gene links
Show Anatomy links
Effects of acamprosate on neuronal receptors and ion channels expressed in Xenopus oocytes.
Reilly MT
,
Lobo IA
,
McCracken LM
,
Borghese CM
,
Gong D
,
Horishita T
,
Harris RA
.
???displayArticle.abstract???
Acamprosate (calcium acetylhomotaurinate) has proven to be a moderately effective pharmacological adjunct for the treatment of alcoholism. However, the central nervous system mechanism by which acamprosate reduces alcohol relapse remains unclear. Here we survey a number of metabotropic receptors, ligand-gated ion channels, and voltage-gated ion channels, to determine if acamprosate has actions at these sites in the central nervous system. Xenopus oocytes were injected with cDNAs or cRNAs encoding metabotropic glutamate receptors 1 and 5, M1 muscarinic receptors, glycine alpha1 homomeric and alpha1beta1 heteromeric receptors, gamma-aminobutyric acid A (GABA(A)alpha4beta3delta, alpha4beta3gamma2s, and alpha1beta2gamma2s) receptors, vanilloid receptor 1, and various combinations of alpha and beta subunits of voltage-gated Na+ channels. Electrophysiological responses were measured using two-electrode voltage clamp parameters after activation with agonists or voltage steps (for the voltage-gated channels). Acamprosate (0.1 to 100 microM) was pre-applied for 1 minute, followed by co-application with agonist. Acamprosate was also applied with ethanol to determine if it altered ethanol responses at some of these receptors and channels. None of the receptors or ion channels responded to acamprosate alone. Acamprosate also failed to alter the activation of receptors or channels by agonists or after activation of voltage-gated channels. There was no effect of acamprosate on ethanol responses at GABA(A)alpha1beta2gamma2s receptors or Na+ channels. Acamprosate does not significantly modulate the function of these receptors and ion channels at clinically relevant concentrations. Thus, the clinical effectiveness of acamprosate in the treatment of alcoholism is not likely due to direct effects on these receptors or ion channels.
Anton,
Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.
2006, Pubmed
Anton,
Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.
2006,
Pubmed
Berton,
Acamprosate enhances N-methyl-D-apartate receptor-mediated neurotransmission but inhibits presynaptic GABA(B) receptors in nucleus accumbens neurons.
1998,
Pubmed
Boismare,
A homotaurine derivative reduces the voluntary intake of ethanol by rats: are cerebral GABA receptors involved?
1984,
Pubmed
Borghese,
The delta subunit of gamma-aminobutyric acid type A receptors does not confer sensitivity to low concentrations of ethanol.
2006,
Pubmed
,
Xenbase
Chester,
Effects of acamprosate on sensitization to the locomotor-stimulant effects of alcohol in mice selectively bred for high and low alcohol preference.
2001,
Pubmed
Cole,
Acamprosate, but not naltrexone, inhibits conditioned abstinence behaviour associated with repeated ethanol administration and exposure to a plus-maze.
2000,
Pubmed
Dahchour,
Effects of ethanol on extracellular amino acid levels in high-and low-alcohol sensitive rats: a microdialysis study.
2000,
Pubmed
De Witte,
Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action.
2005,
Pubmed
Harris,
Acamprosate inhibits the binding and neurotoxic effects of trans-ACPD, suggesting a novel site of action at metabotropic glutamate receptors.
2002,
Pubmed
Heilig,
Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms.
2006,
Pubmed
Johnson,
Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects.
2003,
Pubmed
Kotlinska,
N-methyl-D-aspartate and group I metabotropic glutamate receptors are involved in the expression of ethanol-induced sensitization in mice.
2006,
Pubmed
Lhuintre,
Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics.
1985,
Pubmed
Littleton,
Pharmacological mechanisms of naltrexone and acamprosate in the prevention of relapse in alcohol dependence.
2003,
Pubmed
Madamba,
Acamprosate (calcium acetylhomotaurinate) enhances the N-methyl-D-aspartate component of excitatory neurotransmission in rat hippocampal CA1 neurons in vitro.
1996,
Pubmed
Mason,
Treatment of alcohol-dependent outpatients with acamprosate: a clinical review.
2001,
Pubmed
Mason,
A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone.
2002,
Pubmed
McGeehan,
The anti-relapse compound acamprosate inhibits the development of a conditioned place preference to ethanol and cocaine but not morphine.
2003,
Pubmed
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Minami,
Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes.
1998,
Pubmed
,
Xenbase
Morley,
Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial.
2006,
Pubmed
Naassila,
Mechanism of action of acamprosate. Part I. Characterization of spermidine-sensitive acamprosate binding site in rat brain.
1998,
Pubmed
Olive,
Interactions between taurine and ethanol in the central nervous system.
2002,
Pubmed
Popp,
Interaction of acamprosate with ethanol and spermine on NMDA receptors in primary cultured neurons.
2000,
Pubmed
Rammes,
The anti-craving compound acamprosate acts as a weak NMDA-receptor antagonist, but modulates NMDA-receptor subunit expression similar to memantine and MK-801.
2001,
Pubmed
,
Xenbase
Sanna,
Ethanol inhibits the function of 5-hydroxytryptamine type 1c and muscarinic M1 G protein-linked receptors in Xenopus oocytes expressing brain mRNA: role of protein kinase C.
1994,
Pubmed
,
Xenbase
Shiraishi,
Effects of alcohols and anesthetics on recombinant voltage-gated Na+ channels.
2004,
Pubmed
,
Xenbase
Soyka,
Use of acamprosate and opioid antagonists in the treatment of alcohol dependence: a European perspective.
2003,
Pubmed
Spanagel,
The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption.
2005,
Pubmed
Stalcup,
A treatment model for craving identification and management.
2006,
Pubmed
Trevisani,
Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1.
2002,
Pubmed
Zeise,
Acamprosate (calciumacetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors.
1993,
Pubmed
al Qatari,
Acamprosate is neuroprotective against glutamate-induced excitotoxicity when enhanced by ethanol withdrawal in neocortical cultures of fetal rat brain.
2001,
Pubmed
