NAS181 is a potent and selective antagonist of rat 5-HT1B receptor, with a Ki of 47 nM. NAS181 shows 13-fold selectivity for r5-HT1B over bovine 5-HT1B receptor (Ki=630 nM). NAS181 increases the 5-HT turnover and the synaptic concentration of 5-HT by inhibiting terminal r5-HT1B autoreceptors[2].In Vitro: NAS181 has very low affinities (Ki>3000 nM) for all other receptors examined, including 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7, α1-, α2-, and β-adrenoceptors, and dopamine D1 and D2.
NAS181 (10-1000 nM) dose-dependently potentiates the K+-stimulated [3H]-5-HT release in preloaded rat occipital cortical slices.In Vivo: NAS181 (1-10 mg/kg; s.c.) dose-dependently increases acetylcholine (ACh) release in the frontal, ventral hippocampus cortex and VHipp.
NAS181 (20 mg/kg; s.c.) enhances the 5-HT turnover in four rat brain regions (hypothalamus, hippocampus, striatum, and frontal cortex) with about 40%.
NAS181 (3 mg/kg; s.c.) produces a significant increase in the number of wet dog shakes in rats.