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Updated: Sep 28, 2026

Paradigms for Pharmacological Characterization of C. elegans Synaptic Transmission Mutants
Published on: August 18, 2008
NMDA receptor subtype selectivity: eliprodil, polyamine spider toxins, dextromethorphan, and desipramine selectively
1Preclinical Research Department, Synthélabo Recherche, Rueil-Malmaison, France.
Abstract:
NMDA receptor stimulation concomitantly increases the release of [14C]acetylcholine and [3H]-spermidine from rat striatal slices in vitro. The NMDA-induced release of both acetylcholine and spermidine was blocked with equal potency by the NMDA channel blocker phencyclidine (0.1-10 microM). However, certain other channel blockers, including dextromethorphan (1-100 microM), which antagonized NMDA-evoked acetylcholine release without affecting NMDA-evoked spermidine release, and dextrorphan (1-100 microM) and memantine (1-100 microM), which block NMDA-evoked acetylcholine release more potently than NMDA-evoked spermidine release, showed greater selectivity of action. As previously shown for ifenprodil, eliprodil (SL82.0715; 1-100 microM) blocked NMDA-evoked acetylcholine but not spermidine release. This selectivity is also observed for other agents interacting with the polyamine site(s) on the NMDA receptor, including arcaine (1-1,000 microM), philanthotoxin343, and argiotoxin636 (10 microM) and was also noted for desipramine (1-100 microM). The NMDA-induced release of acetylcholine and spermidine is likely to be mediated by different native NMDA receptor subtypes, and several NMDA antagonists may be candidates for a selective action at a particular NMDA receptor subtype.
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