Pharmacological studies on novel muscarinic agonists, 1-oxa-8-azaspiro[4.5]decane derivatives, YM796 and YM954

Add time:07/27/2019    Source:sciencedirect.com

We have investigated the pharmacological profiles of the novel muscarinic agonists, 1-oxa-8-azaspiro[4.5]decane derivatives, YM796 (2,8-dimethyl-3-methylene) and YM954 (2-ethyl-8-methyl-3-oxo). These compounds, like the putative M1 agonists, RS86 and AF102B, inhibited [3H]pirenzepine binding to cerebral cortical membranes in the micromolar range and weakly inhibited [3H]quinuclidinyl benzylate binding to cerebellar membranes. Their (-) isomers had Hill coefficients lower than 1.0 (±)-YM796, (±)-YM954 and RS86, but not AF102B, stimulated phosphoinositide hydrolysis in hippocampal slices, an effect which is mainly linked to M1 receptors. (±)-YM796 (0.031 mg/kg p.o.) and (±)-YM954 (0.016 mg/kg p.o.) reversed the cognitive impairment in nucleus basalis magnocellularis-lesioned rats in a passive avoidance task more effectively than did RS86 and AF102B. Similar results were obtained in scopolamine-treated rats. Finally, (±)-YM796 was weaker than (±)-YM954 and RS86 in the induction of tremor, hypothermia and contraction of isolated ileum, which are mainly mediated by M2 and/or M3 receptors. These results suggest that (±)-YM796, (±)-YM954 and RS86 have M1 agonistic activity in central nervous system and that (±)-YM796 has relatively weak M2 and/or M3 agonistic activity.

We also recommend Trading Suppliers and Manufacturers of 2-ethyl-8-methyl-3-oxo-1-oxa-8-azaspiro(4,5)decane (cas 132041-83-9). Pls Click Website Link as below: cas 132041-83-9 suppliers

Prev:A green method for the synthesis of novel spiro compounds: Enhancement of antibacterial properties of caffeic acid through electrooxidation in the presence of barbituric acid derivatives
Next:Electrical microstructures of CaTiO3-Bi0.5Na0.5TiO3 microwave ceramics with high permittivity (εrmax ∼487))