205242-48-4Relevant articles and documents
(R)-(+)-2-[[[3-(morpholinomethyl)-2H-chromen-8-yl]oxy]methyl]morpholine methanesulfonate: A new selective rat 5-hydroxytryptormine(1b) receptor antagonist
Berg, Stefan,Larsson, Lars-Gunnar,Rényi, Lucy,Ross, Svante B.,Thorberg, Seth-Olof,Thorell-Svantesson, Gun
, p. 1934 - 1942 (2007/10/03)
In the search for new 5-hydroxytryptamine (5-HT) receptor antagonists it was found that the compound (R)-(+)-2-[[[3-(morpholinomethyl)-2H-chromen-8- yl]oxy]methyl]morpholine methanesulfonate, (R)-25, is a selective rat 5- hydroxytryptamine(1B) (r5-HT(1B)) receptor antagonist. The binding profile showed a 13-fold preference for r5-HT(1B) (Ki = 47 ± 5 nM; n = 3) vs bovine 5-HT(1B) (Ki = 630 nM; n = 1) receptors. The compound had very low affinity for other monoaminergic receptors examined. The r5-HT(1B) receptor antagonism was demonstrated by the potentiation of the K+-stimulated release of [3H]- 5-HT from superfused rat brain slices in vitro, an effect that was antagonized by addition of 5-HT to the superfusion fluid. (R)-25 at 20 mg/kg sc enhanced the 5-HT turnover in four rat brain regions (hypothalamus, hippocampus, striatum, and frontal cortex) with about 40% measured as the 5- HTP accumulation after decarboxylase inhibition with 3- hydroxybenzylhydrazine. At 3 mg/kg sc (R)-25 produced a significant increase in the number of wet dog shakes in rats, a 5-HT(2A)/5-HT(2C) response that was abolished by depletion of 5-HT after pretreatment with the tryptophan hydroxylase inhibitor p-chlorophenylalanine. The observations show that (R)- 25, by inhibiting terminal r5-HT(1B) autoreceptors, increases the 5-HT turnover and the synaptic concentration of 5-HT.
