NMDA RECEPTOR SUBTYPE SELECTIVITY - ELIPRODIL, POLYAMINE SPIDER TOXINS, DEXTROMETHORPHAN, AND DESIPRAMINE SELECTIVELY BLOCK NMDA-EVOKED STRIATAL ACETYLCHOLINE BUT NOT SPERMIDINE RELEASE

NMDA receptor stimulation concomitantly increases the release of [C-14 ]acetylcholine and [H-3]-spermidine from rat striatal slices in vitro. The NMDA-induced release of both acetylcholine and spermidine was blo cked with equal potency by the NMDA channel blocker phencyclidine (0.1 -10 mu M). However, certain other channel blockers, including dextrome thorphan (1-100 mu M), which antagonized NMDA-evoked acetylcholine rel ease without affecting NMDA-evoked spermidine release, and dextrorphan (1-100 mu M) and memantine (1-100 mu M), which block NMDA-evoked acet ylchotine release more potently than NMDA-evoked spermidine release, s howed greater selectivity of action. As previously shown for ifenprodi l, eliprodil (SL82.0715; 1-100 mu M) blocked NMDA-evoked acetylcholine but not spermidine release. This selectivity is also observed for oth er agents interacting with the polyamine site(s) on the NMDA receptor, including arcaine (1-1,000 mu M), philanthotoxin(343), and argiotoxin (636) (10 mu M) and was also noted for desipramine (1-100 mu M). The N MDA-induced release of acetylcholine and spermidine is likely to be me diated by different native NMDA receptor subtypes, and several NMDA an tagonists may be candidates for a selective action at a particular NMD A receptor subtype.