Acamprosate (calciumacetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors

Zeise, Marc L.; Kasparov, S; Capogna, Marco; Zieglgänsberger, W.

doi:10.1016/0014-2999(93)90682-8

Cited by 162 publications

(68 citation statements)

References 11 publications

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“…Thus, acamprosate produced a modest nonsignificant decrease in EPSP amplitude in approximately half of the recorded cells. A similar observation was made in an earlier in vitro recording study in rat neocortical neurons (Zeise et al, 1993). Harris et al (2002) showed that acamprosate has binding and functional characteristics similar to group I mGluR antagonists, in particular to mGluR5.…”

Section: Calcium and Acamprosate R Spanagel Et Alsupporting

confidence: 78%

Acamprosate Produces Its Anti-Relapse Effects Via Calcium

Spanagel

Vengeliene

Jandeleit³

et al. 2013

Neuropsychopharmacol

126

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Alcoholism is one of the most prevalent neuropsychiatric diseases, having an enormous health and socioeconomic impact. Along with a few other medications, acamprosate (Campral-calcium-bis (N-acetylhomotaurinate)) is clinically used in many countries for relapse prevention. Although there is accumulated evidence suggesting that acamprosate interferes with the glutamate system, the molecular mode of action still remains undefined. Here we show that acamprosate does not interact with proposed glutamate receptor mechanisms. In particular, acamprosate does not interact with NMDA receptors or metabotropic glutamate receptor group I. In three different preclinical animal models of either excessive alcohol drinking, alcohol-seeking, or relapse-like drinking behavior, we demonstrate that N-acetylhomotaurinate by itself is not an active psychotropic molecule. Hence, the sodium salt of N-acetylhomotaurinate (i) is ineffective in alcohol-preferring rats to reduce operant responding for ethanol, (ii) is ineffective in alcohol-seeking rats in a cue-induced reinstatement paradigm, (iii) and is ineffective in rats with an alcohol deprivation effect. Surprisingly, calcium salts produce acamprosatelike effects in all three animal models. We conclude that calcium is the active moiety of acamprosate. Indeed, when translating these findings to the human situation, we found that patients with high plasma calcium levels due to acamprosate treatment showed better primary efficacy parameters such as time to relapse and cumulative abstinence. We conclude that N-acetylhomotaurinate is a biologically inactive molecule and that the effects of acamprosate described in more than 450 published original investigations and clinical trials and 1.5 million treated patients can possibly be attributed to calcium.

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Section: Calcium and Acamprosate R Spanagel Et Alsupporting

confidence: 78%

Acamprosate Produces Its Anti-Relapse Effects Via Calcium

Spanagel

Vengeliene

Jandeleit³

et al. 2013

Neuropsychopharmacol

126

View full text Add to dashboard Cite

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“…Therefore, this medication reduces the toxicity induced by glutamate. 8 It seems that acamprosate also reduces calcium reuptake induced by neuronal glutamate, suppresses ethanol-conditioned responses in dependent animals, even in those with prolonged abstinence, reduces the aversive effects of alcohol withdrawal, inhibits the cerebral hyperexcitability induced by glutamate and inhibits the genic expression of c-fos. 9 It seems to have also a serotonergic and beta-adrenergic action.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of acamprosate in the treatment of alcohol-dependent outpatients

Baltieri

Andrade

2003

Rev. Bras. Psiquiatr.

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Objective: To evaluate the efficacy and security of acamprosate in the treatment of 75 men, aged 18 to 59 years, with diagnosis of alcohol dependence according to the ICD-10. Methods: Double-blind, placebo-controlled study, 24-week long. After a one-week detoxification period, patients were randomly divided in two groups: the first group received acamprosate (six tablets of 333 mg/d for 12 weeks) and the second group received placebo (six tablets for 12 weeks). After the first 12 weeks, patients continued the follow-up for further 12 weeks without medication. Results: Patients who were receiving acamprosate showed significantly higher continuous abstinence time within the 24 weeks of treatment compared with patients who were assigned to placebo treatment (p=.017). Twenty-five percent of patients who were receiving acamprosate and 20% of the placebo-treated patients dropped out. Few side-effects were reported in both groups. Conclusion: Acamprosate proved to be safe and effective in treating alcohol-dependent patients and to maintain the abstinence during 24 weeks.Alcoholism. Pharmacological treatment. Acamprosate.Objetivo: Avaliar a eficácia e a segurança do acamprosato no tratamento ambulatorial de setenta e cinco pacientes do sexo masculino, com idade entre 18 e 59 anos, com diagnóstico de dependência de álcool pelo CID-10. Métodos: Trata-se de estudo duplo-cego controlado e randomizado, com duração de 24 semanas. Após um período de desintoxicação de 1 semana, os pacientes foram divididos aleatoriamente em dois grupos: o primeiro grupo recebeu acamprosato (seis comprimidos de 333 mg por dia durante 12 semanas), e o segundo recebeu placebo (seis comprimidos por dia durante 12 semanas). Após as primeiras 12 semanas, os pacientes continuaram o tratamento por mais 12 semanas sem uso de medicação. Resultados: Os pacientes que receberam acamprosato mostraram maior tempo de abstinência contínua ao longo das 24 semanas de tratamento quando comparados aos que receberam placebo (p=0,017). 25% dos pacientes que estavam recebendo acamprosato e 20% dos pacientes que estavam recebendo placebo abandonaram o tratamento. Poucos efeitos colaterais foram registrados em ambos os grupos. Conclusão: O acamprosato mostrou ser seguro e eficaz no tratamento de pacientes dependentes de álcool e na manutenção da abstinência durante 24 semanas.Alcoolismo. Tratamento farmacológico. Acamprosato. Abstract Keywords ResumoDescritores 157

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“…It has been shown to cross the blood-brain barrier and to have neuropharmacological actions (Boismare et al 1984;Chabenat et al 1988;Daoust et al 1992). Acamprosate reduces the postsynaptic efficacy of excitatory amino acid neurotransmitters and lowers neuronal excitability in the neocortex of the rat (Zeise et al 1993). More recent data show that acamprosate may act postsynaptically to increase the n-methyl-d-aspartate (NMDA) component of excitatory transmission to principal neurons in both hippocampal CAl and nucleus accumbens (Madamba et al 1996;Berton et al in press).…”

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confidence: 99%