Substances that directly or indirectly increase excitation are powerful convulsants. For example, application of saline containing a lower than physiological concentration of Mg2+ relieves the normal block of the ion channels gated by N-methyl-D-aspartate (NMDA)-preferring excitatory amino acid receptors, and thus considerably enhances the synap-tic excitation of cells. Application of kainic acid, an agonist of non-NMDA excitatory amino acid receptors, is also widely used to trigger seizures in whole animals, by injection either into the cerebral vesicles or directly into the tissue. The release of endogenous excitatory amino acids can also be triggered by increasing the excitability of neurons with substances that block repolarizing K+ conductances. Neurons have perhaps hundreds of such K+ conductances, and numerous antagonists of these channels are effective convul-sants, including tetraethylammonium, 4-amminopyridine, and various naturally occurring peptide toxins. Finally, modulators of central cholinergic synaptic function are also employed as convulsants, including direct agonists such as pilocarpine as well as acetylcholinesterase inhibitors, and are believed to act by increasing neuronal excitability.
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