Muscarinic receptor 1 allosteric modulators stimulate colorectal emptying in dog, mouse and rat and resolve constipation

Background Because M1 muscarinic receptors are expressed by enteric neurons, we investigated whether positive allosteric modulators of these receptors (M1PAMs) would enhance colorectal propulsion and defecation in dogs, mice, and rats. Methods The potencies of the M1PAMs, T662 or T523, were investigated using M1 receptor‐expressing CHO cells. Effectiveness of M1PAMs on defecation was investigated by oral administration in mice and rats, by...