Abstract
The effects of memantine, an adamantane derivative, on neuromuscular transmission in the frog sartorius muscle preparation were studied by measuring the endplate current (EPC) by the voltage clamp method. Memantine (0.5–50 μM) reduced the peak amplitude and shortened the duration of the EPC, and the membrane voltage-peak EPC relationship became non-linear. Since it decreased the quantal height of the EPC without affecting the mean quantal content, the effects were considered to be mainly postsynaptic. Noise analysis revealed that memantine decreased the mean lifetime of the ACh-activated channel. In addition, lineweaver-Burk analysis of the response to ionophoretically applied carbamylcholine showed that memantine acted essentially as a linear mixed-type inhibitor. Thus memantine seems to block neuromuscular transmission by reacting with the ACh receptor-ion channel complex in both the open and closed states.
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