Related Experiment Video
Updated: Aug 6, 2025

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
Published on: September 20, 2016
Conformationally Restricted σ1 Receptor Antagonists from (-)-Isopulegol
Luca Blicker1, Rafael González-Cano2, Erik Laurini3
1Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstraße 48, D-48149 Münster, Germany.
Abstract:
Antagonists at σ1 receptors have great potential for the treatment of neuropathic pain. Starting from monoterpene (-)-isopulegol (1), aminodiols 8-11 were obtained and transformed into bicyclic 13-16 and tricyclic ligands 19-22. Aminodiols 8-11 showed higher σ1 affinity than the corresponding bicyclic 13-16 and tricyclic derivatives 19-22. (R)-configuration in the side chain of aminodiols (8 and 10) led to higher σ1 affinity than (S)-configuration (9 and 11). 4-Benzylpiperidines (b-series) revealed higher σ1 affinity than 4-phenylbutylamines (a-series). Aminodiol 8b showed very high σ1 affinity (Ki = 1.2 nM), excellent selectivity over σ2 receptors, and promising logD7.4 (3.05) and lipophilic ligand efficiency (5.87) values. Molecular dynamics simulations were conducted to analyze the σ1 affinity and selectivity on an atomistic level. In the capsaicin assay, 8b exhibited similar antiallodynic activity to the prototypical σ1 antagonist S1RA. The antiallodynic activity of 8b was removed by co-application of the σ1 agonist PRE-084, proving σ1 antagonism being involved in the antiallodynic effect.
More Related Videos
Related Concept Videos
Opioid Receptors: Overview
Drug-Receptor Interaction: Agonist
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
The Two-State Receptor Model
The binding affinity of a drug determines its interaction with...
Disubstituted Cyclohexanes: cis-trans Isomerism
In cyclohexane, the substituents can occupy different positions generating distinct isomers....
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement

