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Since a schizophrenia drug, the first in decades with an innovative mechanism of action, gained US regulatory approval in September, some researchers have proclaimed a new era for psychiatric medicine. About half a dozen similar drugs — for schizophrenia, Alzheimer’s disease and other conditions involving the brain — are in various stages of development, most in early-stage clinical trials. But the success of these medicines is not a given. Last week, a trial of a highly anticipated schizophrenia drug reported disappointing results.
For decades, schizophrenia drugs worked in essentially the same way. They blunted the activity of dopamine, a chemical involved in the disorder’s hallmark symptoms, such as hallucinations and delusions. The new kid on the block is KarXT, sold as Cobenfy. It targets muscarinic receptors and leads to antipsychotic and cognitive benefits. “I don’t think I’ve ever seen this much buzz and excitement over a new approach in psychiatry in my career,” says Jeffrey Conn, a pharmacologist at Vanderbilt University in Nashville, Tennessee who was one of the company’s scientific co-founders.
KarXT’s success in winning US regulatory approval has revived interest in muscarinic drugs. “Drug discovery is coming back to psychiatry,” says Arthur Christopoulos, a molecular pharmacologist at Monash University in Melbourne, Australia, who was involved in the development of KarXT.