The effect of the muscarinic M₁ receptor antagonist biperiden on cognition in medication free subjects with psychosis

The acetylcholine muscarinic M-1 receptor has been implicated in both psychosis and cognition. Post-mortem research has shown reduced muscarinic M-1 receptor density in 25% of chronic patients with schizophrenia. It is unknown whether reduced M-1 receptor density is related to cognitive symptoms of psychosis. We investigated the role of the M-1 receptor in separate cognitive domains in subjects with a psychotic disorder using a muscarinic M-1 antagonist as an acute pharmacological challenge. 33 young subjects with a psychotic disorder and 30 gender, age and IQ matched healthy controls were enrolled. All participants completed a comprehensive cognitive test battery twice: once after placebo and once after oral administration of 4 mg. biperiden (M-1 antagonist). The order of drug administration was counterbalanced. Biperiden significantly negatively influenced both verbal (p