Lidocaine effects on brain mitochondrial metabolism in vitro.
Both lidocaine and anoxia inhibit rapid axonal transport. In an attempt to elucidate the mechanism of this action of lidocaine, its effect on mitochondrial respiration was studies. The local anesthetic produces a dose-dependent inhibition of oxygen consumption (50 per cent inhibition at 8mM) by porcine brain mitochondria when glutamate, but not when succinate, serves as the substrate. This indicates electron transport is blocked at the NADH dehydrogenase level. Potent uncoupling of oxidative phosphorylation is observed with both substrates. All of the effects are readily reversible upon removal of the anesthetic. It is concluded that lidocaine apparently inhibits rapid axonal transport by depressing oxidative metabolism.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003864:Depression, Chemical; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D013552:Swine
D008012:Lidocaine; D009247:NADH, NADPH Oxidoreductases