Interaction of i.v. anaesthetic agents with 5-HT3 receptors.
Using N1E-115 neuroblastoma cells as an experimental model, we have examined if four commonly used i.v. anaesthetic induction agents interact with 5-HT3 receptors. Specifically, we tested the hypothesis that the antiemetic effects of propofol may result from 5-HT3 receptor antagonism. Binding of tropisetron (a 5-HT3 selective reference compound), etomidate, ketamine, thiopentone and propofol to 5-HT3 receptors was assessed by measuring the displacement of [3H]BRL 43694 from whole N1E-115 cells. The rank order potency (Ki) was tropisetron (1.7 (SEM 0.2) nmol litre-1) >> etomidate (83.(4) mumol litre-1) > or = ketamine (97 (4) mumol litre-1) > thiopentone (177 (9) mumol litre-1) > propofol (819 (171) mumol litre-1). With the exception of thiopentone these effects were outside the clinical range and suggest that anaesthetic agents are unlikely to interact directly with 5-HT3 receptors, and that other mechanism(s) must underlie the antiemetic effects of propofol.
Appadu
B L
BL
University Department of Anaesthesia, Leicester Royal Infirmary.
Lambert
D G
DG
D018686:Anesthetics, Intravenous / Q000378:metabolism*; D000818:Animals; D000932:Antiemetics / Q000378:metabolism; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000378:metabolism; D017829:Granisetron / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D007649:Ketamine / Q000378:metabolism; D051379:Mice; D015742:Propofol / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D013874:Thiopental / Q000378:metabolism; D000077526:Tropisetron; D014407:Tumor Cells, Cultured
D018686:Anesthetics, Intravenous; D000932:Antiemetics; D005045:Etomidate; D017829:Granisetron; D007211:Indoles; D007649:Ketamine; D015742:Propofol; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013874:Thiopental; D000077526:Tropisetron