Chemistry is an experimental science, and the best way to enjoy it and learn about it is performing experiments.Introducing a new discovery about 873-83-6, Name is 6-Aminopyrimidine-2,4(1H,3H)-dione, molecular formula is , belongs to pyrimidines compound. In a document, author is Kantas, Boglarka, Formula: C4H5N3O2.
In Silico, In Vitro and In Vivo Pharmacodynamic Characterization of Novel Analgesic Drug Candidate Somatostatin SST4 Receptor Agonists
Background: Somatostatin released from the capsaicin-sensitive sensory nerves mediates analgesic and anti-inflammatory effects via its receptor subtype 4 (SST4) without influencing endocrine functions. Therefore, SST4 is considered to be a novel target for drug development in pain, especially chronic neuropathy which is a great unmet medical need. Purpose and Experimental Approach: Here, we examined the in silico binding, SST4-linked G protein activation and beta-arrestin activation on stable SST4 expressing cells and the effects of our novel pyrrolo-pyrimidine molecules (20, 100, 500, 1,000, 2,000 mu g center dot kg(-1)) on partial sciatic nerve ligation-induced traumatic mononeuropathic pain model in mice. Key Results: The novel compounds bind to the high affinity binding site of SST4 the receptor and activate the G protein. However, unlike the reference SST4 agonists NNC 26-9100 and J-2156, they do not induce beta-arrestin activation responsible for receptor desensitization and internalization upon chronic use. They exert 65-80% maximal anti-hyperalgesic effects in the neuropathy model 1 h after a single oral administration of 100-500 mu g center dot kg(-1) doses. Conclusion and Implications: The novel orally active compounds show potent and effective SST4 receptor agonism in vitro and in vivo. All four novel ligands proved to be full agonists based on G protein activation, but failed to recruit beta-arrestin. Based on their potent antinociceptive effect in the neuropathic pain model following a single oral administration, they are promising candidates for drug development.
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Reference:
Pyrimidine | C4H4N2 – PubChem,
,Pyrimidine – Wikipedia