Natural products and their (semi-)synthetic forms in treatment of migraine: History and current status.

Migraine may be described as a headache with moderate to extreme pain that is often accompanied by incapacitating neurological symptoms. It is estimated that 12% of the world population suffers from migraine. Although a number of drugs have been used for treatment of migraine, most of these are not effective for every patient and may have undesirable side-effects. Thus there is an enormous unmet need in current migraine therapy for discovering safer and more effective agents.The information summarized in this review was obtained through extensive literature review and search of relevant books and articles with the use of Web of Knowledge and SciVerse Scopus databases.Greater understanding of the molecular mechanisms underlying the etiopathogenesis of migraine is helpful in identifying novel targets for antimigraine drugs such as cannabinoid, histamine, and melatonin receptors. In the past, natural product-derived constituents have served as an invaluable source of numerous medicinally useful antimigraine agents and it may be expected that further promising drug candidates from natural products will be discovered for antimigraine pharmacotherapy with better efficacy and fewer adverse-effects.The discovery of novel targets in migraine therapy has opened new horizons for compounds that have not been clinically tested or that previously failed in clinical trials as potential antimigraine drugs. Ginkgolide B, melatonin, histamine, oxytocin, various ribosomal peptide toxins, kavalactones, devil's claw-derived compounds, salvinorin A and petasin are among those agents that show considerable promise as novel drugs in migraine prevention and treatment. It is necessary to conduct more research to better understand their antimigraine action, to confirm their effectiveness and safety, and to introduce them into clinical practice.