Novel Approaches to the Development of Antimigraine Drugs: A Focus on 5-HT2A Receptor Antagonists

Abstract

The review is devoted to promising directions of the search for chemical compounds which can be used as the basis for the development of new drugs for migraine treatment. It considers promising biological targets, whose effects are capable of eliminating the manifestations of acute migraine attacks, and also indicates the main existing developments in the form of chemical compounds and drug prototypes interacting with these targets, including those that will soon enter or are at the stage of clinical trials. In particular, preclinical and clinical data on compounds whose effects are determined by the influence on the calcitonin gene-related peptide (CGRP) receptors, serotonin 5-HT_2A and 5-HT_1F receptors, NO-synthase, orexin and glutamate receptors, are discussed. The review focuses on the description of 5-HT_2A receptors as a promising target for the development of novel antimigraine drugs. Information about the structural features of this serotonin receptor subtype, the localization and functions is given; also it involves the pharmacological capabilities of new substances affecting 5-HT_2A receptors. The final part of the review is devoted to new trends in the search for 5-HT_2A antagonists among compounds synthesized based on a serotonin bioisostere, benzimidazole.