Synthesis of heteroaromatic tropeines and heterogeneous binding to glycine receptors

G. Maksay, Zoltán Vincze, Péter Nemes

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Heteroaromatic carboxylic esters of (nor)tropine were synthesized. Tropine esters displaced [3H]strychnine binding to glycine receptors of rat spinal cord with low Hill slopes. Two-site displacement resulted in nanomolar IC50,1 and micromolar IC50,2 values, and IC50,2/IC50,1 ratios up to 615 depending on the heteroaromatic rings and N-methyl substitution. Nortropeines displayed high affinity and low heterogeneity. IC50,1 and IC50,2 values of tropeines did not correlate suggesting different binding modes/sites. Glycine potentiated only the nanomolar displacement reflecting positive allosteric interactions and potentiation of ionophore function. Affinities of three (nor)tropeines were different for glycine receptors but identical for 5-HT3 receptors.

Original languageEnglish
Pages (from-to)6872-6878
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number19
DOIs
Publication statusPublished - Oct 1 2009

Fingerprint

Glycine Receptors
Inhibitory Concentration 50
Esters
Receptors, Serotonin, 5-HT3
Strychnine
Ionophores
Glycine
Rats
Substitution reactions
tropine
Spinal Cord
Binding Sites

Keywords

  • (Nor)tropeines
  • 5-HT receptors
  • [H]Strychnine binding
  • Binding heterogeneity

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Synthesis of heteroaromatic tropeines and heterogeneous binding to glycine receptors. / Maksay, G.; Vincze, Zoltán; Nemes, Péter.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 19, 01.10.2009, p. 6872-6878.

Research output: Contribution to journalArticle

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