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Published on: August 16, 2018
Synthesis of heteroaromatic tropeines and heterogeneous binding to glycine receptors
Gábor Maksay1, Zoltán Vincze, Péter Nemes
1Department of Molecular Pharmacology, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, H-1525 Budapest, PO Box 17, Hungary. maksay@chemres.hu
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.
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