21 Bethanechol 22 Neostigmine
Neostigmine stimulates GI motility throughout the length of the human GI tract. Neostigmine increases gastric emptying65 and both colonic phasic and tonic activity in healthy volunteers.64 Importantly, neostigmine also stimulates colonic transit. The ability to stimulate propulsive activity has been utilized in clinical medicine, where neostigmine has been used to benefit patients with conditions such as acute colonic pseudo-obstruction and postoperative ileus.
Z-338 (23) is a muscarinic M1/M2 receptor antagonist that increases ACh release from nerve terminals in the stomach, stimulating upper gut motility.66 Z-338 appears to increase gastric motor activity in dogs and rats, but a significant effect on gastric emptying is only observed when this parameter is first inhibited pharmacologically.67 In dyspeptic patients, Z-338 appears to have little effect on gastric emptying.68
KW-5092 (24) enhances the release of enteric ACh and may also have cholinesterase inhibitory activity. In animals, KW-5092 stimulates motility along the length of the GI tract, without evoking the behavioral and cardiovascular side effects seen with neostigmine.69,70
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