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 [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.
Nankai
M
M
Preclinical Research Department, Synthélabo Recherche, Rueil-Malmaison, France.
Fage
D
D
Carter
C
C
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D003915:Dextromethorphan / Q000494:pharmacology; D007210:Indoleacetic Acids; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013095:Spermidine / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology
D007210:Indoleacetic Acids; D010636:Phenols; D010648:Phenylacetates; D010880:Piperidines; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; D013111:Spider Venoms; C558368:argiotoxin-636; C074003:philanthotoxin 343; D016202:N-Methylaspartate; D003915:Dextromethorphan; D000109:Acetylcholine; D003891:Desipramine; D013095:Spermidine; C058083:eliprodil