Tetraethylammonium (TEA) is a molecule found to be a weakagonist of the muscle‐type nicotinic receptor. Since receptor activation occurs as isolated bursts, it has been proposed that the receptors have a very low channel‐opening rate constant when bound to TEA.[2]
Lidocaine, alocal anesthetic, 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.[3]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.[3] 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 causingnon-competitive inhibition and restricting the channel from opening.[4]
Benzocaine andtetracaine are alsolocal anesthetics that have an inhibitory effect on the muscle‐type nicotinic receptor.Benzocaine is a permanently uncharged species that inhibits the receptor by plugging the pore of the opened channel.[5]Tetracaine is a permanently positively charged species. It can bind to the receptor at different sites in both the open and closed conformations.[6] Both of these local anesthetics enhance nAChRdesensitization.[5][6]
^abCobo, Raúl; Nikolaeva-Koleva, Magdalena; Alberola-Die, Armando; Fernández-Ballester, Gregorio; González-Ros, José Manuel; Ivorra, Isabel; Morales, Andrés (15 July 2020). "Mechanisms of Blockade of the Muscle-Type Nicotinic Receptor by Benzocaine, a Permanently Uncharged Local Anesthetic".Neuroscience.439:62–79.doi:10.1016/j.neuroscience.2019.05.043.hdl:10045/107949.ISSN1873-7544.PMID31158437.S2CID171092620.
