lysergamide and Mental-Disorders

While the use of ergot alkaloids in folk medicine has been practiced for millennia, systematic investigations on their therapeutic potential began about 100 years ago. Subsequently, Albert Hofmann's discovery of lysergic acid diethylamide (LSD) and its intense psychedelic properties garnered worldwide attention and prompted further studies of this compound class. As a result, several natural ergot alkaloids were discovered and unnatural analogs were synthesized, and some were used to treat an array of maladies, including Alzheimer's and Parkinson's disease. While LSD was never commercially approved, recent clinical studies have found it can be an innovative and effective treatment option for several psychiatric disorders. Ongoing biosynthetic and total synthetic investigations aim to understand the natural origins of ergot alkaloids, help develop facile means to produce these natural products and enable their continued use as medicinal chemistry lead structures. This review recounts major developments over the past 20 years in biosynthetic, total synthetic, and pharmaceutical studies. Many ergot alkaloid biosynthetic pathways have been elucidated, with some of them subsequently applied toward "green" syntheses. New chemical methodologies have fostered a fast and efficient access to the ergoline scaffold, prompting some groups to investigate biological properties of natural product-like ergot alkaloids. Limited pharmaceutical applications have yet to completely bypass the undesirable side effects of ergotism, suggesting further studies of this drug class are likely needed and will potentially harness major therapeutic significance.

Topics: Amides; Animals; Chemistry Techniques, Synthetic; Chemistry, Pharmaceutical; Dopamine Agonists; Ergolines; Ergot Alkaloids; Green Chemistry Technology; Hallucinogens; Heterocyclic Compounds, 4 or More Rings; History, 20th Century; History, 21st Century; Humans; Lysergic Acid Diethylamide; Mental Disorders

Topics: Humans; Lysergic Acid Diethylamide; Mental Disorders; Mescaline; Psychotherapy

Topics: Humans; Lysergic Acid Diethylamide; Mental Disorders; Psychotherapy; Psychotic Disorders