Glutamate Release

Inhibition of glutamate release is another means of functionally dampening excessive glutamate-mediated excitation in pathological states. Agents that block glutamate release—mainly anticonvulsants such as phenytoin, lamotrigine, and zonisamide—are generally believed to do so by interfering with the activity of Na+ or Ca2+ channels in nerve terminals (4,175,176), although there is recent evidence for more complex effects on the release machinery (177,178). Interestingly, these drugs may preferentially inhibit glutamate release as opposed to GAB A release (179). In addition, agents that interact with adenosine receptors and other presynaptic receptors, including mGluRs, can reduce glutamate release. In the case of adenosine, there is also a preferential effect on excitatory versus inhibitory synapses. Several glutamate release inhibitors are in various phases of development as shown in Table 7.

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