Investigating Extended Linker Analogues of Risperidone for Treatment of Multiple Sclerosis

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.