Purinergic receptor inhibitor discovery and application has demonstrated the potential for therapeutic intervention, as demonstrated by pharmacological research. Few chemical modalities have been authorized for use in clinical settings, despite the fact that breakthroughs in crystallography and chemical biology have increased the knowledge of purinergic signaling and its consequences in disease. The many research projects and pharmaceutical movements that sustain dynamic P2X receptor programs over decades are evidence of the therapeutic values and academic persistence in purinergic study. P2X7R is an intriguing therapeutic target and possible biomarker for inflammation. Although several companies like Merck and AstraZeneca have published patents on P2X3 antagonists, the search for P2X7R antagonists has not stopped. Numerous pharmaceutical companies have disclosed different scaffolds, and some molecules are presently being studied in clinical studies.