Synthesis and biological activity of argiotoxin 636 and analogues: selective antagonists for ionotropic glutamate receptors.

More discerning than the parent: Analogues of the polyamine toxin argiotoxin 636 (shown docked in the ion channel of an ionotropic glutamate (iGlu) receptor; N blue, O red) distinguish subtypes of iGlu receptors. Depending on which of the two internal amine groups is replaced with a methylene group, the analogue inhibits one or other of two receptor subtypes as potently as the natural compound, which itself inhibits both subtypes nonselectively.