Pharmacological characterization of a novel 5-HT4 receptor agonist, TS-951, in vitro.
The pharmacological effect of a novel selective 5-HT4 receptor agonist, TS-951 (N-[endo-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]oct-3-yl]-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide) was investigated in vitro. TS-951 potently inhibited specific [3H]GR113808 binding both in guinea-pig striatum and in mouse brain. The affinity of TS-951 for the 5-HT4 receptor was higher than those of other agonists, 5-HT, cisapride, mosapride and renzapride. On the longitudinal muscle of the guinea-pig ileum, TS-951 caused a concentration-dependent increase in the amplitude of electrically induced submaximal twitch contractions. On the longitudinal muscle of the guinea-pig distal colon, TS-951 also caused concentration-dependent contractions. TS-951 is a high-affinity, selective and potent 5-HT4 receptor agonist. This compound therefore can be considered as a useful pharmacological tool for investigating 5-HT4 receptor-mediated events.
Kajita
S
S
Pharmacology Lab., Pharmaceut. Res. Lab., Taisho Pharmaceut. Co. Ltd, Ohmiya, Saitama, Japan.
Ito
C
C
Kawamura
R
R
Yasuda
S
S
Isobe
Y
Y
Fukushima
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology
D007211:Indoles; D011804:Quinolines; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C426443:TS951; D044422:Receptors, Serotonin, 5-HT4; C082871:GR 113808