Cerebral Monoamines and Lidocaine Toxicity in Rats

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Abstract
The effect of alterations in whole brain monoamine content on the plasma lidocaine concentration resulting in seizures was studied in rats. Reductions in brain monoamine content was produced by treatment with reserpine, p-chlorophenylalanine (PCPA) or .alpha.-methyl p-tyrosine (AMPT). Reserpine depleted norepinephrine (NE) and dopamine (DA) by 75% and serotonin (5HT) by 54%; PCPA reduced brain 5HT 56% without changing NE and DA; AMPT reduced brain NE and DA by 54 and 60%, respectively, without altering 5HT content. Treatment with 5-hydroxytryptophan, a serotonin precursor combined with the peripheral decarboxylase inhibitor RO4-4602 [benserazide] increased brain 5HT content by 400% without changes in DA and NE. Whole brain NE concentrations were assayed fluorometrically, DA brain concentrations were assayed by HPLC [high pressure liquid chromatography] and lidocaine concentrations in plasma were determined by gas chromatography. Plasma lidocaine concentrations at the onset of convulsions were elevated significantly only by drugs causing serotonin depletion increasing to 128% of control with reserpine treatment and 139% of control with PCPA treatment. Depletion of NE and DA had no effect on the lidocaine seizure threshold. Increases in brain 5HT caused a small but not statistically significant decrease to 94% of control in the mean plasma lidocaine concentration at seizure onset.

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