Pridopidine

Pridopidine (Huntexil, formerly ACR16, also ASP2314) is an experimental drug candidate belonging to a class of agents known as dopidines, which act as dopaminergic stabilizers in the central nervous system. These compounds may counteract the effects of excessive or insufficient dopaminergic transmission, and are therefore under investigation for application in neurological and psychiatric disorders characterized by altered dopaminergic transmission, such as Huntington's disease (HD). Pridopidine (Huntexil, formerly ACR16, also ASP2314) is an experimental drug candidate belonging to a class of agents known as dopidines, which act as dopaminergic stabilizers in the central nervous system. These compounds may counteract the effects of excessive or insufficient dopaminergic transmission, and are therefore under investigation for application in neurological and psychiatric disorders characterized by altered dopaminergic transmission, such as Huntington's disease (HD). Pridopidine is in late-stage development by Teva Pharmaceutical Industries who acquired the rights to the product from its original developer NeuroSearch in 2012. In April 2010, NeuroSearch announced results from the largest European phase 3 study in HD carried out to date (MermaiHD). The MermaiHD study examined the effects of pridopidine in patients with HD and the results showed after six months of treatment, pridopidine improved total motor symptoms, although the primary endpoint of the study was not met. Pridopidine was well tolerated and had an adverse event profile similar to placebo. The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have both indicated they will not issue approval for pridopidine to be used in human patients on the basis of the MermaiHD and HART trials, and a further, positive phase 3 trial is required for approval. Dopidines, a new class of pharmaceutical compounds, act as dopaminergic stabilizers, enhancing or counteracting dopaminergic effects in the central nervous system. They have a dual mechanism of action, displaying functional antagonism of subcortical dopamine type 2 (D2) receptors, as well as strengthening of cortical glutamate and dopamine transmission. Dopidines are, therefore, able to regulate both hypoactive and hyperactive functioning in areas of the brain that receive dopaminergic input (i.e. cortical and subcortical regions). This potential ability to restore the cortical–subcortical circuitry to normal suggests dopidines may have the potential to improve symptoms associated with several neurological and psychiatric disorders, including HD. In vitro studies demonstrate pridopidine exerts its effects by functional antagonism of D2 receptors. However, pridopidine possesses a number of characteristics that differentiate it from traditional D2 receptor antagonists (agents that block receptor responses). Pridopidine is less likely to produce extrapyramidal symptoms, such as akinesia (inability to initiate movement) and akathisia (inability to remain motionless), than dopamine antagonists (such as antipsychotics). Furthermore, pridopidine displays no detectable intrinsic activity, differentiating it from D2 receptor agonists and partial agonists (agents that stimulate receptor responses). Pridopidine, therefore, differs from D2 receptor antagonists, agonists and partial agonists.