Similar antagonistic effects of Ca N-acetylhomotaurinate on depression of motor activity and lethality induced by acetaldehyde or ethanol.
Among several taurine derivatives, Ca N-acetylhomotaurinate (Ca AOTA) appears to be the most active anti-acetaldehyde and anti-alcohol agent. Studies of the antagonism of the hypomotility induced by high intravenous doses of acetaldehyde or ethanol in mice and of the lethality of high intragastric doses of acetaldehyde in rats show its superiority which appears logical after systematic studies of these derivatives and their components. The reinforcing action of the nervous activity due to N-acetylation of these sulfonic aminoacids differs according to the target. Since Ca AOTA is the most active against acetaldehyde and ethanol toxicity, this central nervous action first relies on its effects on neuromodulators, neuromediators and cations primarily involved in the mechanisms of alcohol dependence through its taurine (TA) structure, its gamma-aminobutyric acid (GABA) agonist actions, its anti-opioid receptor "naloxone-like" effects and its possible activity as a subcellular Ca carrier. Ca AOTA may also intervene through its high membrane stabilizing effect. Compared with the other compounds, it appears to be the most active both in vitro on the erythrocyte membrane of the rabbit and on the human amnion membrane and ex vivo on the alcoholic rat's erythrocyte membrane. Among several taurine derivatives similarly efficient in toxicity of both acetaldehyde and ethanol, Ca AOTA is the best. Its efficiency against the most toxic metabolite of ethanol may specifically rely on Ca and TA dependence of acetaldehyde-dehydrogenase or on an aspecific mechanism such as the role of free radical scavenger due to its taurine structure. Ca AOTA appears to be a promising drug against alcoholism because of its effects on the multiple targets involved in the mechanism of alcohol dependence. A large multicentric coordinated trial has effectively confirmed the reliability of these pharmacological speculations.
Cons. d'Endocrinol. et Mal. Métabol., CHU Cochin Port Royal, Paris, France.
J
J
Durlach
P
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Rinjard
H
H
Sprince
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GG
Smith
D000077443:Acamprosate; D000079:Acetaldehyde / Q000008:administration & dosage / Q000378:metabolism; D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism; D000603:Amino Acids, Sulfur / Q000494:pharmacology; D000818:Animals; D002412:Cations / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000603:Amino Acids, Sulfur; D002412:Cations; D013654:Taurine; D000431:Ethanol; D000079:Acetaldehyde; D000077443:Acamprosate