Pharmacological Characterization of Indisetron Hydrochloride, as a Novel 5-HT3 Receptor Antagonist
|
Accession number;05A0015058
|
| Title;Pharmacological Characterization of Indisetron Hydrochloride, as a Novel 5-HT3 Receptor Antagonist |
| Author;
TANIGUCHI SUGURE
(Nisshinkyorinseiyaku)
WATANABE FUMIKO
(Nisshinkyorinseiyaku)
HAGIHARA KOICHIRO
(Nisshinkyorinseiyaku)
|
Journal Title;Japanese Pharmacology & Therapeutics
|
Journal Code:Z0947A
|
ISSN:0386-3603
|
|
VOL.32;NO.11;PAGE.789-797(2004)
|
| Figure&Table&Reference;FIG.4, TBL.5, REF.23 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;The effects of indisetron hydrochloride (indisetron) on 5-HT3, 5-HT4 and other receptors were investigated. The inhibitory action on 5-HT3 receptor: Indisetron inhibited the binding of [3H] GR65630 to the rat cerebral cortex membrane. The Ki, value was 1.82 nmol/L and the affinity was close to granisetron, ondansetron or azasetron. Indisetron also inhibited the contraction of the guinea-pig colon induced by 2-Me-S-HT. The IC50 was 2.3 * 10-8mo1/L and the activity was approximately 4, 16 or 52 times more potent than that of granisetron, ondansetron or azasetron, respectively. Indisetron reduced 2-Me-5-HT-induced bradycardia (BJR), possibly through its 5-HT3 antagonistic activity in rat. The ED50 was 0.024mg/kg and the activity was equally potent for azasetron and over 20 times stronger than that of granisetron or ondansetron. The inhibitory effect of indisetron on BJR was lasted for 24 hours after the 1mg / kg oral administration in rat. The inhibitory action on 5-HT4 receptor: The relaxation of the rat esophageal tunica muscularis mucosa by 5-MeOT was inhibited by indisetron. The pA2 was 7.01 and the activity was approximately three times more potent than tropisetron. The action to other receptors: Indisetron had affinity to benzodiazepine receptor (Ki: 0.29 .MU.mol/L). However, the affinity was 100 times weaker than that of 5-HT3 receptor. Indisetron (10-4mol/L) showed no affinity to other receptors ; 5-HT1, 5-HT2, dopamine-D1, dopamine-D2, adrenaline-.ALPHA.1, adrenaline- .ALPHA.2, adrenaline-.BETA. receptors. These results indicate that indisetron possesses 5-HT3 and 5-HT4 receptor antagonistic activity. (author abst.) |
|
|
|
Related Articles;
|
|
