title: Differential effect of tetracaine and bupivacaine on catecholamine and 5-hydroxytryptamine turnover.
abstract: The effect of the local anesthetics, tetracaine and bupivacaine, on monoamine oxidase (MAO) activity of rat brain and on the major steps of catecholamine and 5-hydroxytryptamine (5-HT) turnover was examined. The IC50 of tetracaine for MAO-A and MAO-B inhibition was 1.2 microM and 19.5 microM, respectively. Up to 2.5 mM bupivacaine was without effect on either form of MAO. None of the following activities in rat brain or adrenal medulla were inhibited by 5-2500 microM of tetracaine or bupivacaine: catecholamine-O-methyltransferase, tyrosine hydroxylase, dopamine-beta-hydroxylase. Tetracaine caused only a moderately potent inhibition of synaptosomal uptake of norepinephrine (NE) (IC50 14 microM), dopamine (IC50 37 microM) and 5-HT (IC50 45 microM). The potent and specific MAO inhibition by tetracaine, in association with an impaired uptake of synaptosomal amines, may lead to an increase in the synaptosomal content of neurotransmitter amines, such as 5-HT and NE, with possible antinociceptive consequences.
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002045:Bupivacaine / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013748:Tetracaine / Q000494:pharmacology*
chemical_list: D001596:Benzylamines; D008996:Monoamine Oxidase Inhibitors; D013748:Tetracaine; D012701:Serotonin; C030796:benzylamine; D004298:Dopamine; D009638:Norepinephrine; D002045:Bupivacaine