Abstract |
In Suncus murinus, various emetic responses and the anti-emetic activity of a new 5-hydroxytryptamine3 (5-HT3) receptor antagonist, GK-128 (2-[(2-methylimidazol-1-yl) methyl benzo[f]thiochromen-1-one monohydrochloride hemihydrate), were investigated. Cancer chemotherapeutic agents, cisplatin and cyclophosphamide, dose-dependently induced emesis of long-lasting duration. The 5-HT3 receptor agonist, 2-methyl-5-HT, and copper sulfate also induced emesis of short duration. However, another 5-HT3 receptor agonist, m-chlorophenylbiguanide, was not consistently emetic. GK-128 inhibited the emetic responses induced by chemotherapeutic agents and 2-methyl-5-HT with similar potency. The anti-emetic action of GK-128 was more potent than that of ondansetron, Y-25130, granisetron and metoclopramide. The order of potency of these drugs, except granisetron, was consistent with that of their 5-HT3 receptor binding affinity in rat cortex. GK-128 failed to inhibit copper sulfate-induced emesis. These data suggest that GK-128 has a potent inhibitory effect on emesis via the 5-HT3 receptor, and that the 5-HT3 receptor involved in emesis in Suncus murinus may be different from the classically defined 5-HT3 receptor in other animals such as rats, dogs and ferrets.
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Authors | C Ito, Y Isobe, H Kijima, Y Kiuchi, H Ohtsuki, R Kawamura, K Tsuchida, S Higuchi |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 285
Issue 1
Pg. 37-43
(Oct 04 1995)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 8846809
(Publication Type: Journal Article)
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Chemical References |
- Antiemetics
- Chromones
- GK 128
- Imidazoles
- Serotonin Antagonists
- Serotonin
- 2-methyl-5-HT
- Copper
- Cyclophosphamide
- Copper Sulfate
- Cisplatin
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Topics |
- Animals
- Antiemetics
(pharmacology)
- Chromones
(pharmacology)
- Cisplatin
(toxicity)
- Copper
(toxicity)
- Copper Sulfate
- Cyclophosphamide
(toxicity)
- Dose-Response Relationship, Drug
- Female
- Imidazoles
(pharmacology)
- Male
- Serotonin
(analogs & derivatives, pharmacology)
- Serotonin Antagonists
(pharmacology)
- Shrews
- Species Specificity
- Vomiting
(chemically induced, prevention & control)
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