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P3‐273: NEUROCHEMICAL AND ELECTROPHYSIOLOGICAL CHARACTERIZATION OF SUVN‐I6107, A NOVEL MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATOR
Author(s) -
Bhyrapuneni Gopinadh,
Daripelli Saivishal,
Kamuju Venkatesh,
Benade Vijay,
Irappanavar Shantaveer M.,
Gandipudi Sudhakar,
Tirumalasetty Chaitanya,
Petlu Surendra,
Subramanian Ramkumar,
Jayarajan Pradeep,
Shinde Anil K.,
Nirogi Ramakrishna
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.1633
Subject(s) - neurochemical , muscarinic acetylcholine receptor , acetylcholine , pharmacology , donepezil , allosteric modulator , chemistry , muscarinic acetylcholine receptor m1 , muscarinic acetylcholine receptor m4 , muscarinic acetylcholine receptor m3 , allosteric regulation , endocrinology , medicine , receptor , biochemistry , dementia , disease
amplitude all showed a decrease in the placebo group, whereas they increased in the PQ912 group, indicating an improved global functional connectivity in the latter. The AEC showed a significant effect (mean change: placebo1⁄4-0.0054 versus PQ9121⁄40.0044, t-test: p1⁄40.025, Cohen’s d1⁄40.45) and the TCR-amp showed a trend (mean change: placebo1⁄4-0.0012 versus PQ9121⁄40.0018, p1⁄40.065, d1⁄40.37). The effect measured by AEC remained significant when corrected for sex, country, ApoE, age and baseline value, and additionally for EEG measures of oscillatory activity (global relative power measures in 5 frequency bands; both ANCOVA models p<0.05). There was no correlation between global relative theta power and AEC (r1⁄40.12, p1⁄40.22). Conclusions: Functional connectivity, measured with AEC, significantly improved with PQ912 treatment compared to placebo. This effect sustained when corrected for demographic variables, baseline value and EEG relative power measures.