[Mechanisms of action and biochemical toxicology of valproic acid].
The first part of this article presents the hypotheses of the mechanism of action of the anti-epileptic drug, valproic acid (VPA). In the case of the GABAergic hypothesis, two major types of mechanism of action have been proposed, one at the pre-synaptic level, the other at the post-synaptic level. The action at the pre-synaptic level brings into play one or more enzymes of the GABA shunt. The action at the postsynaptic level consists of the potentiation of the inhibitory effect of GABA by VPA. This has justified the examination of the possible action of VPA at the level of the postsynaptic GABAergic receptor complex. The non-GABAergic hypotheses have been also considered to explain the anti-epileptic action of VPA, one hypothesis depends on the effects of VPA directly on the membrane, another hypothesis brings into play aspartate, and finally a hypothesis depending on the inhibition of aldehyde reductases. The second part of this article concerns the possible mechanism for the undesirable effects of VPA such as hyperammonaemia, hepatotoxicity and hypoglycaemia. The role played by beta- and omega-oxidation of VPA in the explanation of the undesirable effects of this molecule is particularly discussed.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors; D000641:Ammonia / Q000097:blood; D000818:Animals; D000927:Anticonvulsants; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D005943:Gluconeogenesis / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D014635:Valproic Acid / Q000378:metabolism / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000927:Anticonvulsants; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D000641:Ammonia; D006884:Hydroxybutyrate Dehydrogenase; C019416:4-hydroxybutyrate dehydrogenase; D000445:Aldehyde Oxidoreductases; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase
Mécanismes d'action et toxicologie biochimique de l'acide valproïque.