| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
116-293 |
DRI_Challenge |
denotes |
Palonosetron is the only 5-HT(3) receptor antagonist approved for the treatment of delayed chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic chemotherapy. |
| T2 |
294-491 |
DRI_Approach |
denotes |
Accumulating evidence suggests that substance P (SP), the endogenous ligand acting preferentially on neurokinin-1 (NK-1) receptors, not serotonin (5-HT), is the dominant mediator of delayed emesis. |
| T3 |
492-549 |
DRI_Approach |
denotes |
However, palonosetron does not bind to the NK-1 receptor. |
| T4 |
550-790 |
DRI_Approach |
denotes |
Recent data have revealed cross-talk between the NK-1 and 5HT(3) receptor signaling pathways; we postulated that if palonosetron differentially inhibited NK-1/5-HT(3) cross-talk, it could help explain its efficacy profile in delayed emesis. |
| T5 |
791-920 |
DRI_Approach |
denotes |
Consequently, we evaluated the effect of palonosetron, granisetron, and ondansetron on SP-induced responses in vitro and in vivo. |
| T6 |
921-1110 |
DRI_Background |
denotes |
NG108-15 cells were preincubated with palonosetron, granisetron, or ondansetron; antagonists were removed and the effect on serotonin enhancement of SP-induced calcium release was measured. |
| T7 |
1192-1326 |
DRI_Approach |
denotes |
After preincubation with palonosetron, but not ondansetron or granisetron, the serotonin enhancement of the SP response was inhibited. |
| T8 |
1327-1413 |
DRI_Background |
denotes |
Rats were treated with cisplatin and either palonosetron, granisetron, or ondansetron. |
| T9 |
1414-1636 |
DRI_Background |
denotes |
At various times after dosing, single neuronal recordings from nodose ganglia were collected after stimulation with SP; nodose ganglia neuronal responses to SP were enhanced when the animals were pretreated with cisplatin. |
| T10 |
1637-1751 |
DRI_Approach |
denotes |
Palonosetron, but not ondansetron or granisetron, dose-dependently inhibited the cisplatin-induced SP enhancement. |
| T11 |
1752-1999 |
DRI_Outcome |
denotes |
The results are consistent with previous data showing that palonosetron exhibits distinct pharmacology versus the older 5-HT(3) receptor antagonists and provide a rationale for the efficacy observed with palonosetron in delayed CINV in the clinic. |
