RT Journal Article SR Electronic T1 Pharmacological Properties of Trimebutine and N-Monodesmethyltrimebutine JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1391 OP 1397 VO 289 IS 3 A1 Francois J. Roman A1 Sandrine Lanet A1 Jacques Hamon A1 Gilles Brunelle A1 Anne Maurin A1 Pascal Champeroux A1 Serge Richard A1 Nicole Alessandri A1 Maurice Gola YR 1999 UL http://jpet.aspetjournals.org/content/289/3/1391.abstract AB Trimebutine [2-dimethylamino-2-phenylbutyl-3,4,5-trimethoxybenzoate hydrogen maleate (TMB)] has been demonstrated to be active for relieving abdominal pain in humans. To better understand its mechanism of action, we have tested TMB; nor-TMB, its main metabolite in humans; and their respective stereoisomers for their affinity toward sodium channels labeled by [3H]batrachotoxin, their effect on sodium, potassium, and calcium currents in rat dorsal root ganglia neurons, and their effect on veratridine-induced glutamate release from rat spinal cord slices. TMB has also been tested in an animal model of local anesthesia. TMB (Ki = 2.66 ± 0.15 μM) and nor-TMB (Ki = 0.73 ± 0.02 μM) displaced [3H]batrachotoxin from its binding site with affinities similar to that of bupivacaine (Ki = 7.1 ± 0.9 μM). nor-TMB was found to block veratridine-induced glutamate release with an IC50 value of 8.5 μM, which is very similar to that of bupivacaine (IC50 = 8.2 μM); the effect of TMB was limited to 50% inhibition at 100 μM. TMB and nor-TMB blocked sodium currents in sensory neurons from rat dorsal root ganglia (IC50 = 0.83 ± 0.09 and 1.23 ± 0.19 μM, respectively), whereas no effect was observed on calcium currents at the same concentrations. A limited effect was observed on potassium currents (IC50 = 23 ± 6 at 10 μM) for TMB. In vivo, when tested in the rabbit corneal reflex, TMB displayed a local anesthetic activity 17-fold more potent than that of lidocaine. The American Society for Pharmacology and Experimental Therapeutics