‘’ KarXT returns the focus to the dopamine system—but manipulates it in a newfangled way.
The drug targets part of the brain called the muscarinic acetylcholine system using the compound xanomeline, which stimulates parts of the surface of neurons—called M1 and M4 receptors—to reduce dopamine transmission. Xanomeline had long been known for its efficacy in alleviating psychotic symptoms, but it also carried some unwanted side effects, such as nausea and vomiting. But now biotech company Karuna Therapeutics says it has solved this bug by adding in the drug trospium, which helps control common side effects xanomeline produces when given on its own. In August 2022, the topline results of a Phase 3 trial of about 250 people [reported]
(https://investors.karunatx.com/news-releases/news-release-details/karuna-therapeutics-announces-positive-results-phase-3-emergent) that the drug significantly reduced the severity of schizophrenia symptoms. At the end of the trial, participants were evaluated using the Positive and Negative Syndrome Scale, or PANSS, a widely used assessment in which schizophrenia patients rate the severity of 30 symptoms on a scale of 1 to 7, giving their condition an overall score. The trial reported a 9.6-point reduction in the overall score for those taking the drug compared to a placebo after five weeks—and KarXT showed promise for treating positive as well as negative symptoms. Perhaps most importantly, the drug wasn’t associated with the classic side effects of traditional antipsychotics.‘’
