Synthesis and neurotropic activity of new derivatives of some amino acid hydantoins and their lithium salts

Abstract

Background: Amino acid hydantoins are widely used in various fields, particularly in pharmacy. For example, phenytoin is used to treat generalized epileptic seizures. Objective: This study aims to investigate the neurotropic properties of new amino acid hydantoin derivatives in order to identify new anticonvulsants with psychotropic properties.Methods: The compounds mentioned exhibited anticonvulsant properties that were evaluated through a series of tests: maximal electric shock, pentylenetetrazole, thiosemicarbazide, picrotoxin, strychnine, nicotine, and camphor convulsions on outbred mice. The psychotropic effects of the compounds were assessed through various tests,including the elevated plus maze (EPM), forced swimming, and open field tests. Additionally, their effect on the activity of monoamine oxidase (MAO) was investigated under in vitro conditions. The neurotoxic effect of these compounds was further examined by conducting the ''rotating rod'' test on mice. Results: The five studied compounds, which are byproducts of amino acid hydantoins, along with Phenytoin and their lithium salts, display neurotropic properties, demonstrating anticonvulsant and psychotropic effects. Compounds that inhibit clonic pentylenetetrazole, maximal electroshock generalized tonic convulsions, nicotine, and kamphoraconvulsions, as well as exhibiting antithiosemicarbazide action in animals, display pronounced anxiolytic and behavior-activating effects across various internationally recognized models. Simultaneously, the compounds show antidepressant (evidenced by the "forced swimming" model) and anti-MAO effects. The compounds did notdemonstrate muscle relaxant effects in the doses examined. In certain aspects of their neurotropic properties, the compounds outperformed drugs currently used in the clinic, including Phenytoin, Ethosuximide, and lithium chloride(antimanic drug), among others. Conclusion: Hydantoins derived from DL-tryptophan, DL-β-phenyl-α-alanine, and Phenytoin, along with their corresponding lithium salts, were synthesized. Both the anticonvulsant and psychotropic effects of these substances have been thoroughly studied. In several models, compounds that inhibit maximal electroshock convulsions in animals and clonic pentylenetetrazole also display anxiolytic and behavior-activating effects. These compounds also exhibit antidepressant and anti-MAO effects. The investigated compounds can be used in medicine, as drugs, in the treatment of epilepsy with psychotropic disorders. Keywords: antiepileptic drugs, derivatives of amino acid, lithium salts, neurotropic activity, pentylenetetrazole convulsions.