INTERACTION OF IV ANESTHETIC AGENTS WITH 5-HT3 RECEPTORS

Using N1E-115 neuroblastoma cells as an experimental model, we have ex amined if four commonly used i.v, anaesthetic induction agents interac t with 5-HT3 receptors. Specifically, we tested the hypothesis that th e antiemetic effects of propofol may result from 5-HT3 receptor antago nism. Binding of tropisetron (a 5-HT2 selective reference compound), e tomidate, ketamine, thiopentone and propofol to 5-HT3 receptors was as sessed by measuring the displacement of [H-3]BRL 43694 from whole N1E- 115 cells. The rank order potency (K-i) was tropisetron (1.7 (SEM 0.2) nmol litre(-1)) much greater than etomidate (83 (4) mu mol litre(-1)) greater than or equal to ketamine (97 (4) mu mol litre(-1)) > thiopen tone (177 (9) mu mol litre(-1)) > propofol (819 (171) mu mol litre(-1) ). With the exception of thiopentone these effects were outside the cl inical range and suggest that anaesthetic agents are unlikely to inter act directly with 5-HT3 receptors, and that other mechanism(s) must un derlie the antiemetic effects of propofol.