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Effect of 5-HT3 Antagonists on Isolated Human Pregnant Myometrium: An in-vitro Study
Abstract Number: O2-02
Abstract Type: Original Research
The 5-hydroxytryptamine (HT)3 receptor antagonists are effective antiemetic agents. They have been extensively used peri-operatively during the recent years. Although 5-HT contracts human uterine artery smooth muscle predominately through 5-HT2 receptors, there was evidence of 5-HT3 receptors on the rat uterine preparation. The effect of 5-HT3 receptor antagonists on human myometrial contractility was unclear.
Upon IRB approval, 24 healthy term parturients scheduled for elective cesarean delivery were recruited. All parturients had a lower segment transverse incision which was performed under spinal anesthesia. After the delivery of fetus and placenta, longitudinal section of myometrial tissue was excised from the midline portion of the lower uterine incision. Oxytocin infusion was withheld until the sample myometrium was collected. The myometrial tissue was then placed in Krebs buffer and transported to the research laboratory within 30 minutes. Myometrial strips were randomly allocated to four groups: control group (Group I, n=6), ondansetron group (Group II, n=6), granisetron group (Group III, n=6) and tropisetron group (Group IV, n=6) and mounted on the myograph. 0.9% normal saline (control group) and five incremental concentration of doses (1 ng/mL, 10 ng/mL, 102 ng/mL, 103 ng/mL and 104 ng/mL) of a 5-HT3 antagonist were sequentially microinjected into the bath. The myometrial contractile characteristics after each drug injection, including contractile force, interval and duration, were analyzed.
The 5-HT3 receptor antagonist, including ondansetron, granisetron and tropisetron at concentrations ranging from 1 ng/mL to 104 ng/mL, had no effects on spontaneous contractions of myometrial strips.
Pharmacokinetic studies in human volunteers showed that the therapeutic plasma concentration of ondansetron, granisetron and tropisetron was 80-100 ng/mL, 17-42 ng/mL, and 10-50 ng/mL, respectively. The plasma protein binding percentage of ondansetron, granisetron and tropisetron was approximately 73%,. 65% and 59-70%, respectively. Therefore the concentrations of these 5-HT3 receptor antagonists we investigated in this study were pharmacological or suprapharmacological doses. We confirmed that 5-HT3 antagonists have no effect on human myometrial contractility during the peripartum period.
1. Karlsson, et al. Hum Reprod 1997
2. Ononiwu, et al. Afr J Med Med Sci 2002