Douglas Yao
1 in 4 people with schizophrenia don’t respond to any existing drugs/treatments. In 2024, Cobenfry made waves by becoming the first FDA-approved schizophrenia drug with a totally new mechanism. Rather than blocking dopamine receptors like all previous schizophrenia drugs, it works by activating a different type of receptor - ‘muscarinic receptors.’ Although Cobenfry is very effective in treating psychosis, its new mechanism carries some new side effects - nausea/vomiting, high blood pressure - which arise from off-target effects. In total, there are 5 different muscarinic receptors, and Cobenfry activates all of them. Only activating M4 (and possibly M1) is useful for schizophrenia. Meanwhile, activating M2 and M3 causes so-called ‘cholinergic’ side effects including the ones listed. Because of these side effects, Cobenfry actually consists of two drugs used together. One of them - xanomeline - activates muscarinic receptors and treats the schizophrenia, while the second - trospium - has opposite effects and helps manage the side effects. Even though trospium helps, many of the side effects persist, which have prevented Cobenfry from reaching widespread use. (2/7)
