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Mechanisms of Inhibition
Lidocaine has multiple inhibitory actions on the receptor and analysis of the structure of lidocaine has identified the presence of a hydrophobic aromatic ring and a hydrophilic terminal amine. Diethylamine (DEA), a molecule that mimics the hydrophilic moiety of lidocaine by way of a positively charged amine, has been found to block the channel when the receptor is open restricting the flow of Na+ and K+ ions. 2,6-Dimethylaniline (DMA), a molecule that mimics the hydrophobic moiety of lidocaine, has been found to bind the receptor at inter-subunit crevices of the trans-membrane spanning domain thereby causing non-competitive inhibition and restricting the channel from opening.