Ability of Calcium bis-Acetyl Homotaurine, a GABA Agonist, to Prevent Relapse in Weaned Alcoholics

Lhuintre, J. P.; Moore, N; Saligaut, Christian; Boismare, F; Daoust, M.; Chrétien, Pierre; Tran, Giang N.; Hillemand, B

doi:10.1097/00132586-198606000-00009

Cited by 30 publications

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“…19,20,22 However, other studies were performed using a 3-month treatment period. 25,26 In our study the total treatment period was six months, in the first three months patients received medication and in the following three months patients remained in the treatment without medication.…”

Section: Discussionmentioning

confidence: 93%

“…[19][20][21][22] However, other studies comparing the efficacy of acamprosate and placebo in the treatment of alcoholism did not show any statistically significant difference. [23][24][25] Regarding the medication's safeness, Lhuintre et al 26 found some side-effects, as follows: nausea (four patients of the acamprosate group versus 1 of the placebo group), erectile dysfunction (2 patients of the acamprosate group versus 1 of the placebo group) and pruritus (only 1 patient of the acamprosate group). Whitworth et al 19 reported that among some of the side-effects reported by patients diarrhea was the most frequent one in patients of the acamprosate group, what was statistically significant (p=.021).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Efficacy of acamprosate in the treatment of alcohol-dependent outpatients

Baltieri

Andrade

2003

Rev. Bras. Psiquiatr.

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“…Considering these observations, acamprosate may act on the mGluR5 receptors reducing its positive feedback control over the NMDARs [217]. Although the exact mechanism of action of acamprosate is still a matter of debate, the glutamatergic hypothesis may help to explain many of the effects of acamprosate in human alcohol dependence, especially in the acquisition of cue-elicited drinking behaviours [17,41,80,86,116,117,199].…”

Section: Acamprosatementioning

confidence: 99%

Role of Altered Structure and Function of NMDA Receptors in Development of Alcohol Dependence

Nagy

Kolok²,

Boros³

et al. 2005

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Long-term alcohol exposure gives rise to development of physical dependence on alcohol in consequence of changes in certain neurotransmitter functions. Accumulating evidence suggests that the glutamatergic neurotransmitter system, especially the N-methyl-D-aspartate (NMDA) type of glutamate receptors is a particularly important site of ethanol's action, since ethanol is a potent inhibitor of the NMDA receptors (NMDARs) and prolonged ethanol exposition leads to a compensatory "upregulation" of NMDAR mediated functions supposedly contributing to the occurrence of ethanol tolerance, dependence as well as the acute and delayed signs of ethanol withdrawal.Recently, expression of different types of NMDAR subunits was found altered after long-term ethanol exposure. Especially, the expression of the NR2B and certain splice variant forms of the NR1 subunits were increased in primary neuronal cultures treated intermittently with ethanol. Since NMDA ion channels with such an altered subunit composition have increased permeability for calcium ions, increased agonist sensitivity, and relatively slow closing kinetics, the abovementioned alterations may underlie the enhanced NMDAR activation observed after long-term ethanol exposure. In accordance with these changes, the inhibitory potential of NR2B subunit-selective NMDAR antagonists is also increased, demonstrating excellent potency against alcohol withdrawal-induced in vitro cytotoxicity. Although in vivo data are few with these compounds, according to the effectiveness of the classic NMDAR antagonists in attenuation, not only the physical symptoms,but also some affective and motivational components of alcohol withdrawal, novel NR2B subunit selective NMDAR antagonists may offer a preferable alternative in the pharmacotherapy of alcohol dependence.

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“…Although the precise mechanism of action or cellular target of acamprosate is not fully elucidated, acamprosate appears to modulate N-methyl-D -aspartate (NMDA) receptor activity in the glutamate system, and to inhibit the upregulation of voltage-gated Ca 2 ϩ channels that is induced by chronic alcohol ingestion and states of withdrawal (Allgaier et al 2000;Popp and Lovinger 2000). Thus, acamprosate may act on neurobiological mechanisms that may persist for many months following alcohol withdrawal, and that may contribute to the vulnerability for drinking relapse (Borg 1988).The clinical safety and efficacy of acamprosate was evaluated in 16 placebo-controlled, double-blind trials of 3, 6, or 12 months duration conducted across 11 European countries and involving more than 4,500 male and female outpatients with alcohol dependence (Barrias et al 1997;Besson et al 1998;Chick et al 2000a;Geerlings et al 1997;Gual and Lehert 2001;Ladewig et al 1993;Lhuintre et al 1985Lhuintre et al , 1990Paille et al 1995;Pelc et al 1992Pelc et al , 1997Poldrugo 1997;Rousseaux et al 1996;Sass et al 1996;Tempesta et al 2000;Whitworth et al 1996). Fourteen of 16 trials showed a significant advantage for acamprosate over placebo on abstinence measures.…”

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confidence: 99%

A Pharmacokinetic and Pharmacodynamic Drug Interaction Study of Acamprosate and Naltrexone

Mason

2002

Neuropsychopharmacology

104

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Recent efforts to develop pharmacological interventions for relapse-prevention in newly abstinent alcoholics initially focused on acamprosate (Campral ®, Aotal ®) in Europe and naltrexone (ReVia ®) in the United States of America. Acamprosate and naltrexone have each demonstrated efficacy and safety in randomized, double-blind, placebo-controlled trials in alcohol-dependent outpatient volunteers (Garbutt et al. 1999;Litten and Allen 1998;Mason 2001;Mason and Ownby 2000;Swift 1999). Neither medication interacts with alcohol or has abuse potential or rebound effects when discontinued. Despite these similarities, acamprosate and naltrexone induce their action via very different mecha- Address correspondence to: Barbara Mason, Alcohol Disorders Research Unit, 1400 N.W. 10th Avenue, Suite 307A, Miami, FL 33136. Tel.: (305) 243-4059; E-mail: bjmason246@aol.com Received February 12, 2002; revised April 18, 2002; accepted April 22, 2002. Online publication: 5/7/02 at www.acnp.org/citations/Npp 050702298. N EUROPSYCHOPHARMACOLOGY 2002 -VOL . 27 , NO . 4 Interaction Study of Acamprosate and Naltrexone 597 nisms and may affect different behavioral aspects of alcohol dependence. Acamprosate is a centrally acting synthetic analog of the naturally occurring amino acid neuromediator taurine (Dahchour and de Witte 2000). Chronic alcohol exposure is associated with decreased GABAergic transmission and increased glutamate activity (Grant et al. 1990;Hoffman and Tabakoff 1994). Although the precise mechanism of action or cellular target of acamprosate is not fully elucidated, acamprosate appears to modulate N-methyl-D -aspartate (NMDA) receptor activity in the glutamate system, and to inhibit the upregulation of voltage-gated Ca 2 ϩ channels that is induced by chronic alcohol ingestion and states of withdrawal (Allgaier et al. 2000;Popp and Lovinger 2000). Thus, acamprosate may act on neurobiological mechanisms that may persist for many months following alcohol withdrawal, and that may contribute to the vulnerability for drinking relapse (Borg 1988).The clinical safety and efficacy of acamprosate was evaluated in 16 placebo-controlled, double-blind trials of 3, 6, or 12 months duration conducted across 11 European countries and involving more than 4,500 male and female outpatients with alcohol dependence (Barrias et al. 1997;Besson et al. 1998;Chick et al. 2000a;Geerlings et al. 1997;Gual and Lehert 2001;Ladewig et al. 1993;Lhuintre et al. 1985Lhuintre et al. , 1990Paille et al. 1995;Pelc et al. 1992Pelc et al. , 1997Poldrugo 1997;Rousseaux et al. 1996;Sass et al. 1996;Tempesta et al. 2000;Whitworth et al. 1996). Fourteen of 16 trials showed a significant advantage for acamprosate over placebo on abstinence measures. There are no serious or rate-limiting adverse effects associated with acamprosate. Mild and transient diarrhea is the only drug-related adverse event that differed consistently from placebo across studies. Acamprosate is not metabolized. It is eliminated by the kidneys and is contra-indicated in cases of re...

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Ability of Calcium bis-Acetyl Homotaurine, a GABA Agonist, to Prevent Relapse in Weaned Alcoholics

Cited by 30 publications

References 0 publications

Efficacy of acamprosate in the treatment of alcohol-dependent outpatients

Efficacy of acamprosate in the treatment of alcohol-dependent outpatients

Role of Altered Structure and Function of NMDA Receptors in Development of Alcohol Dependence

A Pharmacokinetic and Pharmacodynamic Drug Interaction Study of Acamprosate and Naltrexone

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