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
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),..View full abstract
This work was supported by the Australian Government: Department of Education, the Cooperative Research Centre for Mental Health, the National Health and Medical Research Council, the Rebecca L. Cooper Medical Research Foundation, One-in-Five and the Victorian Government's Operational Infrastructure Support Programme.