Dexamethasone Has a Central Antiemetic Mechanism in Decerebrated Cats

Abstract

Dexamethasone is an effective antiemetic drug, but its mechanism of action is unclear. We designed this study to investigate the direct antiemetic action of dexamethasone in the medulla of cats. By using an oscillographic vomiting model, decerebrated cats received microinjections of dexamethasone 100 nL (1 microg, n = 7; 0.1 microg, n = 7) into the bilateral nuclei tractus solitarii, which led to a significant prolongation of the latency (1 microg, 6.4 +/- 1.1 min versus 28.2 +/- 4.9 min, P < 0.05; 0.1 microg, 6.7 +/- 1.1 min versus 27.1 +/- 5.0 min, P < 0.05) of the first emetic episode and significantly decreased the frequency of emetic episodes (1 microg, 2.7 +/- 0.8 versus 0.1 +/- 0.4, P < 0.05; 0.1 microg, 2.9 +/- 0.9 versus 0.3 +/- 0.5, P < 0.05) induced by xylazine. Pretreatment with mifepristone, a glucocorticoid receptor antagonist, blocked the antiemetic effect of dexamethasone in the bilateral nuclei tractus solitarii. However, microinjection of dexamethasone into the unilateral nucleus tractus solitarius alone did not alter the latency of the first emetic episode or the frequency of emetic episodes induced by xylazine. Local application of dexamethasone into the area postrema had no effect on the latency of the first emetic episode or the frequency of emetic episodes induced by xylazine. These results suggest that dexamethasone exerts its central antiemetic action through an activation of the glucocorticoid receptors in the bilateral nuclei tractus solitarii in the medulla.

Comparison of caudal and intravenous dexamethasone as adjuvants for caudal epidural block: A double blinded randomised controlled trial

“…[28] Results of our studies are in line with this, we found that the incidence of nausea/vomiting was comparatively low in group receiving dexamethasone 8.6% (3/35) than control group 31.4% (11/35). It is advisable to use, therefore, prophylactic antiemetics to all patients administered caudal epidural with local anaesthetics alone.…”

Glucocorticoid resistance of migration and gene expression in a daughter MDA-MB-231 breast tumour cell line selected for high metastatic potential

“…Despite the common use of glucocorticoids as anti-emetics in cancer patients receiving chemotherapy, the mechanism of action of this effect remains unclear. Several mechanisms have been proposed7 including: decreasing the inflammatory response from chemotherapy or radiation8910; direct actions on the solitary tract nucleus in the central nervous system which receives emetogenic inputs from the afferent sympathetic and parasympathetic nervous systems11; effects on key mediators/receptors in emetic pathways such as 5HT and NK receptors121314; and effects on the hypothalamic-pituitary-adrenal (HPA)-axis15. Rapid glucocorticoid actions related to increased levels of endocannabinoid CB1 ligands may also play a role in the antiemetic effect of glucocorticoids1617.…”

Efficacy of Single Parenteral Dose of Palonosetron Versus Dexamethasone for Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Surgeries Under General Anaesthesia

“…By centrally inhibiting the tractus solitarius nucleus and not the area of postrema in animal's experiments, it exerts its antiemetic property. 6 Slow mode of action facilitates its use at the beginning of a case, which appears superior to latter use. 5 Glucocorticoids bind to intracellular glucocorticoid receptors and exert their effects via gene transcription.…”