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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< 0.001 and p =0.032) and visual learning and memory ( p= 0.028) in both groups. A medication x group interaction effect was found for reasoning and problem solving ( p =0.005). No main or interaction effects were found for other cognitive domains. These results provide further in-vivo evidence that the M 1 receptor is involved in cognitive functioning, particularly verbal and visual memory processes. Lack of differential effects of biperiden between psychotic subjects and healthy controls may suggest that decreased M 1 receptor density is only present in chronic, older schizophrenia patients. However, it remains possible that differential effects of biperiden would be present in more severe cognitive impaired subjects with psychosis after several doses of biperiden instead of a single administration. [ABSTRACT FROM AUTHOR]

Cocaine use affects approximately 13.4 million people, or 0.3% of the world׳s population between 15 and 64 years of age. Several authors have described drug addiction as a disease of the brain reward system. Given that the cholinergic system impacts reward mechanisms and drug self-administration, acetylcholine (ACh) might play an important role in the cocaine addiction process. We evaluated the efficacy of biperiden (a cholinergic antagonist) in reducing craving and the amount used, and in increasing compliance with treatment for cocaine/crack addiction. It was a study double-blind, randomised, placebo-controlled, 8-week trial of 111 cocaine or crack addicted male patients between 18 and 50 years old. Two groups were compared: placebo ( n =55) or biperiden ( n =56) combined with weekly sessions of brief group cognitive-behavioural therapy. The efficacy of treatment was evaluated according to the patients’ compliance and several instruments: the Minnesota Cocaine Craving Scale, the Beck Depression and Anxiety Scales and a questionnaire assessing the amount of drug used. All of the patients attended weekly sessions for two months. We analysed the data considering the patients׳ intention to treat based on our last observation. Of the 56 patients in the biperiden group, 24 completed the treatment (42.8%) compared with only 11 patients in the placebo group (20%), which was a significant difference ( p =0.009). Compliance with treatment was 118% higher in the biperiden group, which was also the group that presented a statistically significant reduction in the amount of cocaine/crack use ( p <0.001). There was statistically significant difference between the craving score in the biperiden group. Pharmacological blockade of the cholinergic system with biperiden is a promising alternative to treat cocaine/crack addiction, helping patients to reduce the amount used and improving compliance with psychotherapy treatment. [ABSTRACT FROM AUTHOR]

Abstract: As perturbations in auditory filtering appear to be a candidate trait marker of schizophrenia, there has been considerable interest in the development of translational rat models to elucidate the underlying neural and neurochemical mechanisms involved in sensory gating. This is the first study to investigate the effects of the non-selective muscarinic antagonist scopolamine, the muscarinic M1 antagonist biperiden and the cholinesterase inhibitor donepezil (also in combination with scopolamine and biperiden) on auditory evoked potentials (AEPs) and sensory gating. In the saline condition, only the N50 peak displayed sensory gating. Scopolamine and biperiden both disrupted sensory gating by increasing N50 amplitude for the S2 click. Donepezil was able to fully reverse the effects of biperiden on N50 sensory gating, but had residual effects when combined with scopolamine; i.e., it enhanced sensory gating by increasing N50 amplitude of the S1 stimulus. Donepezil by itself improved sensory gating by enhancing N50 amplitude of S1, and reducing N50 amplitude of the S2 click. In conclusion, due to its relatively more selective effects biperiden is to be preferred over scopolamine as a means for pharmacologically inducing cholinergic impairments in auditory processing in healthy rats. Changes in auditory processing and sensory gating induced by cholinergic drugs may serve as a translational model for aging instead of schizophrenia. [Copyright &y& Elsevier]