eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2025-12-30 22 4 1430 1442 10.13005/bbra/3452 57337 article Parekh Nirmit Jigneshkumar 1 Patel Mahek Devangbhai 1 Ayyan Dutta 1 Arnab Dutta 1 Debadrita Ghosh 1 Gowri Krishnaperumal 1 Faculty of Medicine and Health Sciences, Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, India. The study of migraine is a neurological condition that may cause headaches, followed by vomiting and sensitivity reactions of light and sound. In this review, we present a comprehensive and systematic analysis of current pathophysiology development strategies to treat migraine, highlighting their mechanisms of action, such as triptans, CGRP antagonists, anti-inflammatory drugs, and antidepressants. In addition, this review explores the pathophysiological mechanisms responsible for monogenic and polygenic migraine disorders, showing the involvement of the trigeminovascular pathway. Migraine is generally categorised into three important types: Migraine with Aura, Migraine without Aura and Hemiplegic migraine. A Migraine is divided into four phases: premonitory phase, aura phase, headache phase, and postdromal phase. Further, we have shown that GPCR, cAMP, CGRP, and PACAP signalling pathways play crucial roles in both physiological and pathophysiological processes. In migraine, cAMP causes inflammation and vasodilation. Increased cAMP levels activate receptors like CGRP and PACAP that trigger migraines. These receptors interact with G proteins to increase cAMP inside the cells. To treat migraine, we used purinergic receptors, which help in lowering the cAMP levels to reduce migraine symptoms. Additionally ,this review highlights, the phosphodiesterases (PDE) activators for migraine treatment, which help in reducing the accumulation of intracellular cAMP levels. Activation of cAMP-selective phosphodiesterases (PDE3 and PDE5) is used in the treatment of migraine. PDE4 acts as a modulator that, on inhibition, leads to elevated cAMP levels and releases the inflammatory neuropeptides like CGRP, which play a major role in migraine by promoting sensitisation of pain pathways. On the other hand, PDE5 is an enzyme that breaks down cGMP levels, which influence the vasodilation of cerebral blood vessels. Excessive vasodilation contributes to migraine headaches by activating pain-sensitive structures in the brain (like the trigeminovascular system). This review highlights the basic pathophysiology of migraine, the effects of inflammatory mediators and their mechanisms.^1,2 https://www.biotech-asia.org/vol22no4/impact-of-various-receptors-gpcr-pacap-cgrp-purinergic-receptors-and-phosphodiesterase-in-migraine/ cAMP; CGRP; Gepants; GPCR; Monoclonal antibodies; PACAP; PDE4; PDE5