Bioorganic & Medicinal Chemistry 2009-10-01

Synthesis of heteroaromatic tropeines and heterogeneous binding to glycine receptors.

Gábor Maksay, Zoltán Vincze, Péter Nemes, Gábor Maksay, Zoltán Vincze, Péter Nemes

Index: Bioorg. Med. Chem. 17(19) , 6872-8, (2009)

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Abstract

Heteroaromatic carboxylic esters of (nor)tropine were synthesized. Tropine esters displaced [(3)H]strychnine binding to glycine receptors of rat spinal cord with low Hill slopes. Two-site displacement resulted in nanomolar IC(50,1) and micromolar IC(50,2) values, and IC(50,2)/IC(50,1) ratios up to 615 depending on the heteroaromatic rings and N-methyl substitution. Nortropeines displayed high affinity and low heterogeneity. IC(50,1) and IC(50,2) 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-HT(3) receptors.