PMID: 1322987Jul 24, 1992Paper

Enantiomeric N-substituted N-normetazocines: a comparative study of affinities at sigma, PCP, and mu opioid receptors

Journal of Medicinal Chemistry
F I CarrollC Sauss

Abstract

The optical antipodes of N-allyl-N-normetazocine (2; SKF 10047, NANM) were the original compounds used for the classification of the sigma receptor as distinct from other receptors such as the PCP (NMDA), opioid, and dopamine receptors. Later studies showed that (+)-N-(dimethylallyl)-N-normetazocine [(+)-4, (+)-pentazocine] was more potent and selective for the sigma receptor. In order to gain additional structure-activity relationship information, several N-substituted N-normetazocine analogs were prepared and evaluated for their sigma-1 ([3H]-(+)-3-PPP or [3H]-(+)-pentazocine), PCP ([3H]TCP), and mu opioid ([3H]DAMGO) receptor binding affinities. (+)-N-Benzyl-N-normetazocine [(+)-10)] possessed subnanomolar affinities for the sigma site, Ki = 0.67. The analog (+)-10 showed greater than 14,000- and 2400-fold selectivity, respectively, for the sigma receptor relative to the PCP and mu opioid receptors. The N-substituted N-normetazocines were enantioselective for the sigma site. The (+)-N-benzyl analog, (+)-10, showed a 55-fold selectivity relative to (-)-10. Analysis of the data also revealed that (+)-normetazocine [(+)-1] [Ki = 30 nM] possessed the highest affinity for the PCP receptor. However, (+)-metazocine [(+)-5] (Ki = 41...Continue Reading

Citations

Nov 25, 2003·Journal of Molecular Graphics & Modelling·Tamara M GundDawoon Jung
Feb 1, 1997·Pharmacology, Biochemistry, and Behavior·X Xu, E F Domino
Dec 13, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G RonsisvalleS Spampinato
May 29, 2016·Pharmacology, Biochemistry, and Behavior·Adam L HalberstadtSusan B Powell
Jun 10, 2015·Organic & Biomolecular Chemistry·Matthias P QuickBernhard Wünsch
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Sep 1, 1996·Pharmazie in unserer Zeit·B Wünsch
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Samuel D BanisterMichael Kassiou
Jun 28, 2021·European Journal of Medicinal Chemistry·Tao ZhuangYin Chen
Apr 3, 2019·Journal of Medicinal Chemistry·Elisabeth KronenbergBernhard Wünsch
Oct 31, 2007·Journal of Medicinal Chemistry·Christian GeigerBernhard Wünsch

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