scholarly journals Safety, pharmacokinetics and quantitative EEG modulation of TAK‐071, a novel muscarinic M1 receptor positive allosteric modulator, in healthy subjects

2021 ◽  
Author(s):  
Wei Yin ◽  
Fahimeh Mamashli ◽  
Derek L. Buhl ◽  
Polyna Khudyakov ◽  
Dmitri Volfson ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Quantitative Eeg ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
M1 Receptor

scholarly journals Widespread Changes in Positive Allosteric Modulation of the Muscarinic M1 Receptor in Some Participants With Schizophrenia

2019 ◽  
Vol 22 (10) ◽  
pp. 640-650 ◽  
Author(s):  
Shaun Hopper ◽  
Geoffrey Mark Pavey ◽  
Andrea Gogos ◽  
Brian Dean
Keyword(s):  
Carboxylic Acid ◽  
Radioligand Binding ◽  
Allosteric Modulation ◽  
Allosteric Modulator ◽  
Allosteric Modulators ◽  
Positive Allosteric Modulator ◽  
M1 Receptor ◽  
Area 6 ◽  
Subcortical Regions

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), hippocampus, and striatum from 40 participants with schizophrenia (20 MRDS and 20 non-MRDS) and 20 controls were used to measure benzyl quinolone carboxylic acid-mediated shift in acetylcholine displacement of [3H]N-methylscopolamine using a novel in situ radioligand binding with autoradiography methodology. Results Compared with controls, participants with schizophrenia had lower levels of specific [3H]N-methylscopolamine binding in all CNS regions, whilst benzyl quinolone carboxylic acid-modulated binding was less in the striatum, Brodmann’s area 6, dentate gyrus, and subiculum. When divided by subgroup, only in MRDS was there lower specific [3H]N-methylscopolamine binding and less benzyl quinolone carboxylic acid-modulated binding in all cortical and subcortical regions studied. Conclusions In a subgroup of participants with schizophrenia, there is a widespread decreased responsiveness to a positive allosteric modulator at the CHRM1. This finding may have ramifications it positive allosteric modulators of the CHRM1 are used in clinical trials to treat schizophrenia as some participants may not have an optimal response.

Rapid and efficient synthesis of a novel cholinergic muscarinic M1 receptor positive allosteric modulator using flash chemistry

2019 ◽  
Vol 17 (35) ◽  
pp. 8166-8174
Author(s):  
Shotaro Miura ◽  
Koichiro Fukuda ◽  
Shinichi Masada ◽  
Hirotsugu Usutani ◽  
Makoto Kanematsu ◽  
...  
Keyword(s):  
Allosteric Modulator ◽  
Efficient Synthesis ◽  
Positive Allosteric Modulator ◽  
M1 Receptor

Continuous flash synthesis of a 2-bromobenzaldehyde derivative from the corresponding 1-bromo-2-iodobenzene derivative is described for rapid and efficient synthesis of a novel cholinergic muscarinic M1 receptor positive allosteric modulator.

P3-273: NEUROCHEMICAL AND ELECTROPHYSIOLOGICAL CHARACTERIZATION OF SUVN-I6107, A NOVEL MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATOR

2006 ◽  
Vol 14 (7S_Part_22) ◽  
pp. P1182-P1182
Author(s):  
Gopinadh Bhyrapuneni ◽  
Saivishal Daripelli ◽  
Venkatesh Kamuju ◽  
Vijay Benade ◽  
Shantaveer M. Irappanavar ◽  
...  
Keyword(s):  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
M1 Receptor ◽  
Electrophysiological Characterization

The muscarinic M1 receptor positive allosteric modulator PQCA improves cognitive measures in rat, cynomolgus macaque, and rhesus macaque

2012 ◽  
Vol 225 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Jason M. Uslaner ◽  
Donnie Eddins ◽  
Vanita Puri ◽  
Christopher E. Cannon ◽  
Jane Sutcliffe ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Cynomolgus Macaque ◽  
Allosteric Modulator ◽  
Cognitive Measures ◽  
Positive Allosteric Modulator ◽  
M1 Receptor

[P1-079]: SUVN-I6107: A NOVEL MUSCARINIC M1 RECEPTOR-POSITIVE ALLOSTERIC MODULATOR (M1-PAM) DEVOID OF CHOLINERGIC SIDE EFFECTS

2017 ◽  
Vol 13 (7S_Part_5) ◽  
pp. P268-P268
Author(s):  
Pradeep Jayarajan ◽  
Renny Abraham ◽  
Sumanth Yathavakilla ◽  
Venkatesh Goura ◽  
Arun Babu Vuyyuru ◽  
...  
Keyword(s):  
Side Effects ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
M1 Receptor
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