Ability of 2-Chloro-N-(1-(3,4-dimethoxyphenyl)propan-2-yl)-2-phenylacetamide to Stimulate Endogenous Nitric Oxide Synthesis

Abstract

Papaverine is one of the isoquinoline alkaloids derived from opium which is a vasodilator and smooth muscle relaxant. Using its chemical structure as a basic model, we synthesized 2-chloro-N-(1-(3,4-dimethoxyphenyl)propan-2-yl)-2-phenylacetamide as an isoquinoline precursor (IQP). Aim: Clarifying the nature of the relationship between IQP as a new biologically active molecule and the neurotransmitters acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5-HT), as well as with the nitric oxide (NO). Materials and methods: The IQP compound was tested on the isolated gastric smooth muscle preparations (SMPs) from rats to determine its effects on spontaneous contractile activity. NO concentration in tissue homogenates was determined, and immunohistochemistry was used to visualize the expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in smooth muscle (SM) cells. Results: The data from the isometric measurements suggest that IQP has an additional specific action affecting the intracellular signaling pathways of 5-HT. Using immunohistochemistry, we found that the combination of 5-HT and IQP affected the density and intensity of nNOS-positive cells, which increase significantly in the myenteric plexus and SM cells. Conclusions: In conclusion, IQP is involved in the regulation of intestinal neurons expressing nNOS, affects the function of nNOS/NO, and, by this mechanism, probably regulates the spontaneous contractile activity of gastric SM.