Investigating Extended Linker Analogues of Risperidone for Treatment of Multiple Sclerosis

<p>Risperidone is a second-generation antipsychotic used to treat psychiatric disorders such as schizophrenia, bipolar disorder and autism. It targets dopamine D2 and serotonin 5-HT2A receptors and has immunomodulatory properties. Multiple sclerosis is a chronic inflammatory disease that affects over 2 million people worldwide and currently has no cure. Recent research at Victoria University of Wellington has shown that risperidone is able to reduce disease severity in mouse models of multiple sclerosis. Further research has demonstrated that truncated and unsaturated analogues of risperidone have varying immunomodulatory effects in immune cells. The current research describes the synthesis and preliminary in vitro testing of four extended-linker analogues of risperidone. Structure-activity relationship studies with neurotropic drugs have shown that altering the length of the alkyl chain found in many of these compounds can have significant effects on receptor binding profiles. Synthesis and cytokine production assays of these analogues begin to provide further insight into how risperidone exerts its immunomodulatory effects and may contribute to the development of new treatments for multiple sclerosis.</p>

Investigating Extended Linker Analogues of Risperidone for Treatment of Multiple Sclerosis

<p>Risperidone is a second-generation antipsychotic used to treat psychiatric disorders such as schizophrenia, bipolar disorder and autism. It targets dopamine D2 and serotonin 5-HT2A receptors and has immunomodulatory properties. Multiple sclerosis is a chronic inflammatory disease that affects over 2 million people worldwide and currently has no cure. Recent research at Victoria University of Wellington has shown that risperidone is able to reduce disease severity in mouse models of multiple sclerosis. Further research has demonstrated that truncated and unsaturated analogues of risperidone have varying immunomodulatory effects in immune cells. The current research describes the synthesis and preliminary in vitro testing of four extended-linker analogues of risperidone. Structure-activity relationship studies with neurotropic drugs have shown that altering the length of the alkyl chain found in many of these compounds can have significant effects on receptor binding profiles. Synthesis and cytokine production assays of these analogues begin to provide further insight into how risperidone exerts its immunomodulatory effects and may contribute to the development of new treatments for multiple sclerosis.</p>

PROMISING DIRECTIONS FOR THE APPLICATION OF PIPERIDINE DERIVATIVES AS STRUCTURAL COMPONENTS OF NEUROTROPIC DRUGS

Piperidine is one of the most common heterocycles, and its derivatives are found in many pharmacological groups, including neurotropic drugs. These compounds are numerous among analgesics, and, in addition to “classical” promedol, fentanyl and its derivatives, the paper presents the results of studying new compounds with analgesic activity and piperidine cycle. Reviews of such piperidine antipsychotics as haloperidol and risperidone have been considered, and new compounds showing antipsychotic activity through their effects on dopamine and serotonin receptors have been elucidated. The data on the influence of methylphenidate on the brain in case of attention deficit/ hyperactivity disorder (ADHD) have been analyzed, which help to understand the disturbances occurring in this disease. Tiagabine has been considered as an antiepileptic agent reducing the number of seizures in resistant forms of partial epilepsy, as well as the activation of microglia and may be effective in neurodegenerative diseases. The last section is devoted to drugs for the treatment of Alzheimer’s disease (AD), namely donepezil, its modifications, and some new compounds potentially capable of inhibiting AD progression through the inhibition of Aβ42 protein synthesis.