Arzneimittelforschung 2010; 60(9): 544-552
DOI: 10.1055/s-0031-1296323
Antiemetics · Gastrointestinal Drugs · Urologic Drugs
Editio Cantor Verlag Aulendorf (Germany)

Arylalkylamine-, β-carboline-, quinolizine- and azecine-derived compounds and their in vitro interaction with the ionotropic 5-HT3 receptor: search for new lead structures

Christoph Enzensperger
1   Institut für Pharmazie, Lehrstuhl für Pharmazeutische/Medizinische Chemie, Friedrich Schiller Universität, Jena, Germany
3   Temporarily at Unilever Centre for Molecular Science Informatics, Department of Chemistry, Lensfield Road, Cambridge, UK
Jochen Lehmann
1   Institut für Pharmazie, Lehrstuhl für Pharmazeutische/Medizinische Chemie, Friedrich Schiller Universität, Jena, Germany
Katrin von Schroetter
2   Institut für Pharmazeutische/Medizinische Chemie, Abteilung Pharmakologie, Westfälische Wilhelms-Universität Münster, Münster, Germany
Anja Riyazi
2   Institut für Pharmazeutische/Medizinische Chemie, Abteilung Pharmakologie, Westfälische Wilhelms-Universität Münster, Münster, Germany
Eugen J. Verspohl
2   Institut für Pharmazeutische/Medizinische Chemie, Abteilung Pharmakologie, Westfälische Wilhelms-Universität Münster, Münster, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 December 2011 (online)


Specific Serotonin receptor agonists and antagonists are marketed with respect to various diseases, most prominently severe emesis. To identify new chemical classes with affinity for the serotonin 5-HT3 channel, several compounds were synthesized which can be structurally classified as arylalkylamines, azecines, quinolizines and β-carbolines. These were tested in three models: 1. direct effect on ileum (overall model for contracting or relaxant effect), 2. antiserotoninergic effects on rat ileum (crude serotonin model), 3. inhibitory effect on the 5-HT3 receptor channel complex expressed in N1E-115 cells (serotonin-induced [14C]guanidinium influx (specific model)). Key findings and conclusion: Several azecine-type compounds exhibit 5-HT3 receptor channel antagonistic properties at concentrations close to that of tropisetron (used as a positive control) and might serve as potential lead structures for the development of further 5-HT3 channel receptor antagonists.

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