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

作者：Enzensperger Christoph^*; Lehmann Jochen; von Schroetter Katrin; Riyazi Anja; Verspohl Eugen J

来源：Drug Research, 2010, 60(9): 544-552.

• Azecine
• beta-Carboline
• 5-HT3 receptor
• Phenylalkylamine
• Quinolizine

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 beta-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 NIE-115 cells (serotonin-induced [C-14]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.

• 出版日期2010