Pharmacodynamics of Alcohol

Early theories of the biological effects of ethanol were based on alterations of lipids in biomembranes (Goldstein et al. 1983 Seeman 1972). Such a nonspecific mechanism provided little guidance for the development of therapeu- 

Other systems also interact with glutamate. Activation of L-type voltagegated calcium channels (VGCC) occurs with NMDA receptor activation. Lamotrigine blocks several ion channels, including P- and N-type VGCC channels, an action that blocks the euphoric effects of ketamine and reduces dysphoric and cognitive effects (Hundt et al. 1998). Other modulatory sites, 

Ethanol acts at 5-HTjg, 5-HT2C, and 5-HT3 receptors (Krystal et al. 2003b). Animal studies have shown that reduction of ethanol consumption is dependent on the presence of the 5-HT3 receptor (Hodge et al. 2004), a 

Findings from animal studies suggest that neuropeptide Y (NPY) may be associated with ethanol consumption. NPY-deficient mice have increased alcohol consumption (Thiele et al. 1998), an effect that is mediated by the Y1 and Y2 receptors (Pandey et al. 2003 Thiele et al. 2000, 2002). It has been suggested that NPY Y1 agonists and Y2 antagonists may have promise in the treatment of alcoholism (Cowen et al. 2004). 

Other peptides that have been linked to the actions of ethanol are corticotropin-releasing factor, urocortin, leptin, cholecystokinin, melanocortins, and galanin (for reviews, see Cowen et al. 2004 Egli 2003 Thiele et al. 2003). 

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Clinically it has been shown that acamprosate can prevent relapse in alcoholics. In a large double-blind, placebo-controlled European study, acamprosate was shown to be effective in the treatment of alcoholism. Thus at the end of a 1-year period of treatment followed by a 1-year period without medication, 39% of the patients were still abstinent compared with 17% of the placebo-treated patients. Its main clinical effect would appear to be due to its anti-craving properties as it does not interfere with the pharmacokinetics or pharmacodynamics of alcohol. Furthermore, it does not have any reinforcing effects or discriminative stimulus properties of its own. Acamprosate has now been registered for the treatment of alcoholism in most European countries. 

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