The selective 5-hydroxytryptamine (5-HT)4-receptor agonist RS67506 enhances lower intestinal propulsion in mice.
Interactions of gastrointestinal prokinetic benzamides with 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptors and the relation to their effects on gastrointestinal propulsion were investigated. Renzapride and zacopride potently inhibited 5-HT3-receptor-mediated contractions in the guinea pig colon, whereas RS67506 (1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-(2-methyl sulphonylamino)ethyl-4-piperidinyl]-1-propanone hydrochloride), a selective 5-HT4-receptor agonist, showed no inhibition. RS67506, renzapride and zacopride all exerted 5-HT4 receptor-mediated relaxation in the carbachol-precontracted rat oesophagus. In mice, RS67506 shortened the whole gut transit time, whereas renzapride and zacopride were reported to prolong it. Gastrointestinal prokinetic benzamides, which are selective for 5-HT4-receptor agonistic over 5-HT3-receptor antagonistic action, may be useful in treating gastrointestinal disorders associated with impaired lower intestinal propulsion such as constipation.
Nagakura
Y
Y
Pharmacological Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Ito
H
H
Kiso
T
T
Naitoh
Y
Y
Miyata
K
K
D000818:Animals; D003106:Colon / Q000187:drug effects; D004947:Esophagus / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044422:Receptors, Serotonin, 5-HT4; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D044422:Receptors, Serotonin, 5-HT4; C107556:RS 67506