Journal article

Widespread Changes in Positive Allosteric Modulation of the Muscarinic M-1 Receptor in Some Participants With Schizophrenia

Shaun Hopper, Geoffrey Mark Pavey, Andrea Gogos, Brian Dean

International Journal of Neuropsychopharmacology | OXFORD UNIV PRESS | Published : 2019

Abstract

BACKGROUND: Preclinical and some human data suggest allosteric modulation of the muscarinic M1 receptor (CHRM1) is a promising approach for the treatment of schizophrenia. However, it is suggested there is a subgroup of participants with schizophrenia who have profound loss of cortical CHRM1 (MRDS). This raises the possibility that some participants with schizophrenia may not respond optimally to CHRM1 allosteric modulation. Here we describe a novel methodology to measure positive allosteric modulation of CHRM1 in human CNS and the measurement of that response in the cortex, hippocampus, and striatum from participants with MRDS, non-MRDS and controls. METHODS: The cortex (Brodmann's area 6),..

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