A series of 17-substituted-3-hydroxy- or 3-alkoxy- analogs of dextromethorphan [(+)-3-methoxy-17-methylmorphinan] was prepared and evaluated for their binding affinities at σ1, σ2, and PCP sites on the NMDA receptor channel, in rat brain. The most potent and σ1-selective compound was 3-ethoxy-17-benzylmorphinan (3e; Ki = 8.0 nM) that was >130 fold selective over σ2 sites and >5000-fold less potent at PCP sites. All of the compounds demonstrated low affinity at σ2 sites (Ki range of ∼0.5 - >10 μM) and at PCP sites (Ki range of ∼0.5 - 98 μM). These compounds may provide useful tools for elucidation of the functional role of σ1 receptors in the central nervous system.
|Original language||English (US)|
|Number of pages||16|
|Journal||Medicinal Chemistry Research|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Organic Chemistry