Highly selective σ1 ligands based on dextromethorphan

Amy Hauck Newman, Jamshed H. Shah, Sari Izenwasser, Brett Heller, Mariena Mattson, Frank C. Tortella

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)102-117
Number of pages16
JournalMedicinal Chemistry Research
Volume6
Issue number2
StatePublished - Dec 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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    Newman, A. H., Shah, J. H., Izenwasser, S., Heller, B., Mattson, M., & Tortella, F. C. (1996). Highly selective σ1 ligands based on dextromethorphan. Medicinal Chemistry Research, 6(2), 102-117.