The anti-emetic activity of GK-128 in Suncus murinus

• Published in: European journal of pharmacology Vol. 285; no. 1; pp. 37 - 43
• Main Authors: Ito, Chika, Isobe, Yoshihiko, Kijima, Haruko, Kiuchi, Yoichi, Ohtsuki, Hiroshi, Kawamura, Reiko, Tsuchida, Katsuharu, Higuchi, Shohei
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04-10-1995; Elsevier
• Subjects: 5-HT 3 receptor; Animals; Antiemetics - pharmacology; Biological and medical sciences; Chromones - pharmacology; Cisplatin - toxicity; Copper - toxicity; Copper Sulfate; Cyclophosphamide - toxicity; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Emesis; Female; GK-128; Imidazoles - pharmacology; Male; Medical sciences; Pharmacology. Drug treatments; Serotonin - analogs & derivatives; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Shrews; Species Specificity; Suncus murinus; Toxicity: digestive system; Vomiting - chemically induced; Vomiting - prevention & control; GK-128; Suncus murinus; Emesis; 5-HT 3 receptor; Antineoplastic agent; Toxicity; Nausea; Vertebrata; Chemotherapy; Mammalia; Treatment; Vomiting; Animal; Digestive diseases; Antagonist; Insectivora; Antiemetic; 5-HT3 receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00372-R

In
Suncus murinus, various emetic responses and the anti-emetic activity of a new 5-hydroxytryptamine
3 (5-HT
3) 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-HT
3 receptor agonist, 2-methyl-5-HT, and copper sulfate also induced emesis of short duration. However, another 5-HT
3 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-HT
3 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-HT
3 receptor, and that the 5-HT
3 receptor involved in emesis in
Suncus murinus may be different from the classically defined 5-HT
3 receptor in other animals such as rats, dogs and ferrets.