当前位置： SCI文献检索 > ANESTHESIA AND ANALGESIA期刊下所有文献 > The pronociceptive effect of ondansetron in the setting of P-glycoprotein inhibition.

The pronociceptive effect of ondansetron in the setting of P-glycoprotein inhibition.

Abstract：

:Ondansetron is a potent antiemetic drug that acts through inhibition of the 5HT3 receptors for serotonin. Minimum alveolar concentration (MAC) for isoflurane is not affected by systemic ondansetron; however ondansetron is a substrate of P-glycoprotein, a transport pump expressed in the blood-brain barrier. Thus, we hypothesized that central nervous system concentrations of ondansetron might be reduced by the P-gp protein. As potent inhibitors of P-gp are in clinical trials to improve access of desirable chemotherapeutic and antibiotic drugs to the central nervous system, we studied the effect of ondansetron in the absence of extrusion by P-gp. Normal rats were given lumbar intrathecal ondansetron or vehicle. P-gp knockout mice and wild-type controls were treated with systemic ondansetron in the presence and absence of clinically used P-gp inhibitors. Nociception was assessed as thermal hindpaw withdrawal latency and immobility was assessed as isoflurane MAC. In rats, intrathecal ondansetron (20 g) increased thermal pain sensitivity by 20.0% +/- 5.8% (P < 0.01). Systemic ondansetron (2 mg/kg) increased pain sensitivity in P-gp knockout mice but had no effect in wild-type mice (P < 0.01). Systemic ondansetron had a small but statistically significant pronociceptive effect after treatment of wild-type mice with the P-gp inhibitor quinidine but not with cyclosporine or verapamil. Isoflurane MAC was not changed by intrathecal ondansetron in rats or systemically administered ondansetron in P-gp knockout mice. Intrathecal ondansetron can enhance thermal pain sensitivity. In the absence of P-gp protein, ondansetron can reach concentrations sufficient to increase pain sensitivity. Even with direct spinal application, ondansetron does not alter isoflurane MAC, supporting the idea that 5HT3 modulation does not play a role in general anesthetic immobility.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Scott JA,Wood M,Flood P

doi

10.1213/01.ane.0000228861.80314.22

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

742-6

issue

eissn

0003-2999

issn

1526-7598

pii

103/3/742

journal_volume

103

pub_type

杂志文章

在线工具

The pronociceptive effect of ondansetron in the setting of P-glycoprotein inhibition.