Abstract
Topiramate has a negative modulatory effect on voltage-gated ion channels involved in neuromuscular junction transmission. To investigate the potential impact of topiramate on muscle contraction, phrenic nerve-hemidiaphragm preparations were used as a neuromuscular junction model. Phrenic nerve-hemidiaphragm preparations were isolated from rats and were mounted in oxygenated Krebs solution. Preparations were stimulated in the presence of topiramate and phenytoin with a rectangular pulse at 0.1 Hertz, 0.3 miliseconds, and 3 miliseconds of duration, forming indirect, direct single, and tetanic muscle contractions, respectively. The expressed tension was isometrically recorded via a force displacement transducer on a polygraph. Topiramate and phenytoin directly and indirectly reduced contractions in a time-dependent manner. By contrast, topiramate, but not phenytoin, showed an excitatory effect on contraction in tetanic potentiation. To our knowledge, our study is the first to show the effects of topiramate on muscle contraction and neuromuscular junction transmission. Topiramate needs to be used with caution in patients with muscle weakness and respiratory problems.
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