title: Effects of local anesthetics on monoamine oxidase, and their membrane effects.
abstract: The effects of various local anesthetics on rat brain and liver monoamine oxidase (MAO) and their antihemolytic and local anesthetic effects were studied. All local anesthetics tested at 1 x 10(-7) M to 1 x 10(-3) M inhibited MAO activity in rat liver mitochondria with 5-hydroxytryptamine (5-HT) as substrate. The order of potency was tetracaine>procaine>dibucaine>lidocaine>prilocaine. Tetracaine and procaine inhibited 5-HT oxidation much more than beta-phenylethylamine (PEA) oxidation. Dibucaine inhibited PEA oxidation as much as 5-HT oxidation. Inhibition of MAO by local anesthetics other than dibucaine was reversible. Tetracaine and procaine inhibited 5-HT oxidation competitively, whereas dibucaine inhibited it non-competitively. Antihemolytic effects were observed with dibucaine and tetracaine at concentrations of 6 x 10(-5) M and 1 x 10(-4), respectively. The order of surface anesthetic potencies was dibucaine>tetracaine>prilocaine>lidocaine>procaine. These results suggest that the inhibition of MAO activities by local anesthetics depends on both electrostatic and hydrophobic interactions between these drugs and enzyme-associated phospholipids or the hydrophobic regions of proteins.
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology; D003315:Cornea / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D004910:Erythrocyte Membrane / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000779:Anesthetics, Local; D008996:Monoamine Oxidase Inhibitors; D003576:Electron Transport Complex IV