[Acamprosate. From pharmacology to therapeutics].
Acamprosate is an homotaurine derivative, structural analogue of Gamma amino butyric acid and upper homologue of taurine. Its crossing through the blood brain barrier is facilitated by acetylation and calcium salification. Acamprosate has a very weak toxicity attributable to the ingested dose of calcium. Acamprosate is a GABAagonist showing pharmacological activity on direct and indirect tests of GABA activity and a high binding capacity with GABA receptors. Acamprosate also shows beta-adrenergic and serotoninergic activity, probably due to its GABAergic activity. Acamprosate is neither and antidepressant, nor a neuroleptic or a tranquillizer. In experimental alcohology, on different animal models (alcohol preferring or alcohol dependent) acamprosate induces a very clear and highly significant reduction of alcohol consumption. This effect is progressive and dose dependent, antagonized by bicuculine which is a GABA agonist. Besides, acamprosate reduces the intensity of the alcohol withdrawal syndrome. Clinical alcohology is a very difficult field for strict methodology in therapeutic trials: determination of inclusion characters, choice of judgment criteria, reduction of the number of drop out and lost subjects, length of evaluation... Different clinical controlled studies, most in double blind against placebo, on patients suffering from signs of physical or psychical alcohol addiction as well as biological modifications due to their ethylic consumption showed beneficial effects of acamprosate (in weaned alcoholics after withdrawal) according to clinical criteria (the number of abstinents after 3 months was doubled: 60% with active drug--30% with placebo) and for biological criteria (Normalization of Gamma Glutamyl Transpeptidase level in blood). The tolerance is good.(ABSTRACT TRUNCATED AT 250 WORDS)
Nalpas
B
B
Unité d'Hépatologie, Hôpital Laënnec, Paris.
Dabadie
H
H
Parot
P
P
Paccalin
J
J
D000077443:Acamprosate; D000437:Alcoholism / Q000188:drug therapy*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004341:Drug Evaluation; D006801:Humans; D011963:Receptors, GABA-A / Q000187:drug effects*; D013654:Taurine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use
D011963:Receptors, GABA-A; D013654:Taurine; D000077443:Acamprosate
L'acamprosate. De la pharmacologie à la clinique.