Effects of Ondansetron and Granisetron on Rocuronium-induced Neuromuscular Blockade in a Rat Phrenic Nerve-hemidiaphragm Preparation. |
Chong Wha Baek, Hyun Kang, Yong Hun Jung, Jung Won Park, Hwa Sung Jung, Yoon Kyung Lee, Hong Seuk Yang |
1Department of Anesthesiology and Pain Medicine, College of Medicine, Chung-Ang University, Seoul, Korea. 2Department of Anesthesiology and Pain Medicine, Kangneung Asan Medical Center, Gangneung, Korea. 3Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea. hsyang@amc.seoul.kr |
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Abstract |
BACKGROUND Both ondansetron and granisetron exert their antiemetic effects via a blockade of the 5-hydroxytryptamine 3 receptor (5-HT(3)R). Because the 5-HT(3)R is a member of a superfamily of ligand-gated ion channels and has structural similarities to the nicotinic acetylcholine receptor (nAChR), a 5-HT(3)R antagonist may also inhibit the nAChR.
This study examined the effects of 5-HT(3)R antagonists, ondansetron and granisetron, on rocuronium-induced neuromuscular blockade in vitro. METHODS Rat phrenic nerve-hemidiaphragm preparations were isolated and allocated randomly into seven groups (control, 1, 10, 100 microgram/ml of ondansetron, 0.1, 1, 10 microgram/ml of granisetron). Two studies were carried out using single twitch responses. In the cumulative dose-response study, rocuronium 1 microgram/ml and each doses of ondansetron or granisetron were administered simultaneously, and incremental 0.5 microgram/ml doses of rocuronium were added to obtain more than 95% neuromuscular twitch inhibition. ED(5), ED(50), ED(90), and ED(95) of rocuronium in each group were calculated using a logistic model. In the partial curarization study, the twitch heights were measured after administering ondansetron or granisetron (10 minutes after administering 3 microgram/ml rocuronium) and were measured 10 minutes later. The 2 twitch heights were then compared. RESULTS In the cumulative dose-response study, ondansetron 100 microgram/ml and granisetron 10 microgram/ml significantly reduced the ED50 of rocuronium (P < 0.05).
There were no intergroup differences in the partial curarization study. CONCLUSIONS High concentration of ondansetron and granisetron enhanced the neuromuscular blockade of rocuronium. Granisetron enhanced the neuromuscular blockade of rocuronium more potently than ondansetron. |
Key Words:
drug interaction; granisetron; neuromuscular blockade; ondansetron; rocuronium |
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