Table 1.
Affinities of dextromethorphan (DM), dextrorphan (DX) and analogs at NMDA, σ1, and σ2 binding sites and their potencies to block NMDA-induced convulsions.
| Compound | NMDA Receptor Ki (nM) |
σ1 Receptor Ki (nM) |
σ2 Receptor Ki (nM) |
NMDA-Induced Seizures ED50 (95% confidence limit) (μg) |
|---|---|---|---|---|
| DX | 460 | 559 | 1128 | 5 (2-11) |
| AHN 1019c | 487 | 1034 | >10,000 | 20 (11-36) |
| AHN 1050 | 1410 | 64 | >1000 | 210 (171-258) |
| AHN 1069 | 1770 | 2078 | >10,000 | 44 (25-76) |
| DM | 3500 | 419 | 2639 | 168 (125-226) |
| AHN 1047 | 11,500 | 2181 | >1000 | >400 |
| AHN 1053 | 27,800 | 24 | 948 | 113 (72-177) |
| AHN 1080 | 40,200 | 8 | 1050 | 186 (125-277) |
Compounds are displayed in order of their NMDA receptor affinity. NMDA receptor affinity was obtained by displacement of [3H]TCP binding. σ1 receptor affinity was determined by the displacement of [3H]SKF 10047 binding in the presence of MK-801. σ2 receptor binding affinities were obtained by displacement of [3H]DTG binding in the presence of (+)-SKF-10047. Binding data are from Newman, et al. (1996).