Long-term potentiation in the presence of NMDA receptor antagonist arylalkylamine spider toxins

The role of the NMDA receptor (NMDAR) in long-term potentiation (LTP) is no w well established. All potent NMDAR antagonists known to date inhibit the induction of LTP at the Schaffer collateral-CA1 pyramidal cell synapse in r at hippocampus, regardless of their site and mechanism of action. Arylalkyl amine toxins are noncompetitive NMDAR antagonists in the mammalian central nervous system (CNS). The synthetic toxins argiotoxin-636 (Arg-636), Joro s pider toxin (JSTX-3), alpha-agatoxin-489 and -505 (Agel-489 and Agel-505) a nd philanthotoxin-433 (delta-PhTX) were found in the present study to have no effect on the induction of LIP in the Schaffer collateral-CA1 pyramidal cell pathway in rat hippocampal slices maintained in vitro. Arylalkylamine toxins represent a class of potent NMDAR antagonists that fail to affect hi ppocampal LTP, and thus provide novel structural leads for the development of NMDAR antagonists that do not impair cognition. (C) 2000 Wiley-Liss, Inc .