A review.The sigma-1 receptor is a 223 amino acid-long protein with a recently identified structure.The sigma-2 receptor is a genetically unrelated protein with a similarly shaped binding pocket and acts to influence cellular activities similar to the sigma-1 receptor.Both proteins are highly expressed in neuronal tissues.As such, they have become targets for treating neurol. diseases, including Alzheimers disease (AD), Huntingtons disease (HD), Parkinsons disease (PD), multiple sclerosis (MS), Rett syndrome (RS), developmental and epileptic encephalopathies (DEE), and motor neuron disease/amyotrophic lateral sclerosis (MND/ALS).In recent years, there have been many pre-clin. and clin. studies of sigma receptor (1 and 2) ligands for treating neurol. disease.Drugs such as blarcamesine, dextromethorphan and pridopidine, which have sigma-1 receptor activity as part of their pharmacol. profile, are effective in treating multiple aspects of several neurol. diseases.Furthermore, several sigma-2 receptor ligands are under investigation, including CT1812, rivastigmine and SAS0132.This review aims to provide a current and up-to-date anal. of the current clin. and pre-clin. data of drugs with sigma receptor activities for treating neurol. disease.