In this context, the multi-target drug approach or network pharmacology emerges as a new step in the development of innovative migraine pharmacotherapy. The design, discovery, and development of new drugs that reach several (instead of unique) specific targets (functional selectivity) involved in the migraine pathophysiology is essential to progress in the migraine treatment and open a new field of study about the main pathways and targets that could synergistically improve the migraine management. In the last 25 years, the development of antimigraine compounds

following the rational drug design (ie, triptans and gepants) has allowed us to advance in the knowledge of specific pathways involved in the Rucaparib cell line migraine pathophysiology.1-4 Certainly, this approach has boosted the pharmacotherapy of several illnesses, making better the specificity of a compound for a specific receptor and avoiding undesirable effects and unspecific actions associated with inherent “promiscuity” of several drugs. Notwithstanding the fact that we have performed and developed a pharmacological arsenal to treat migraine headache, not all patients respond to a specific treatment,4-6 suggesting at the first instance that the key mechanisms related to migraine

relief remain elusive. JAK inhibitor This point appears obvious if we take literally the fact that migraine headache is the product of this website the interaction with complex and multifactorial variables,1-3,7 and the current animal models used to understand its pathophysiology only reflect some characteristics of this disorder. Physiologically speaking, the pain control is a product of functional interactions between multiple anatomical structures, receptors, and neuromediators.[8] Currently, migraine is considered as a debilitating and complex neurological disorder, characterized by recurrent attacks of a moderate to severe throbbing unilateral headache with symptoms such as nausea, vomiting, photophobia, osmophobia, and/or phonophobia and in some cases

preceded by neurological premonitory symptoms.1-3 Indeed, in addition to complex neuronal spinal, supraspinal, and cortical mechanisms,[1, 7] several endogenous and exogenous triggers, as well as genetic and epigenetic factors, are involved.[2, 3] Taken collectively, the number of molecular and anatomical targets that we could manipulate in order to alleviate this disorder is broader. In this context, although it has been claimed for a long time that the intervention of multiple systems simultaneously could be harmful, the design of specific drugs capable of activating several specific signaling pathways (multitarget drug approach) may avoid this problem. In short, this concept refers to the ability of a molecule (instead of a mixture of different molecules) to selectively target multiple receptors and/or mechanisms related to specific clinical conditions.