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The anti-asthmatic drug pranlukast suppresses the delayed-phase vomiting and reverses intracellular indices of emesis evoked by cisplatin in the least shrew (Cryptotis parva).

Authors :
Darmani, Nissar A.
Chebolu, Seetha
Zhong, Weixia
Kim, William D.
Narlesky, Matthew
Adams, Joia
Dong, Fanglong
Source :
European Journal of Pharmacology. Aug2017, Vol. 809, p20-31. 12p.
Publication Year :
2017

Abstract

The introduction of second generation serotonin 5-HT 3 receptor (5-HT 3 ) antagonist palonosetron combined with long-acting substance P neurokinin NK 1 receptor (NK 1 ) antagonists (e.g. netupitant) has substantially improved antiemetic therapy against early- and delayed-phases of emesis caused by highly emetogenic chemotherapeutics such as cisplatin. However, the improved efficacy comes at a cost that many patients cannot afford. We introduce a new class of antiemetic, the antiasthmatic leukotriene CysLT1 receptor antagonist pranlukast for the suppression of cisplatin-evoked vomiting. Pranlukast (10 mg/kg) by itself significantly reduced the mean frequency of vomits (70%) and fully protected least shrews from vomiting (46%) during the delayed-phase of cisplatin (10 mg/kg)-evoked vomiting. Although, pranlukast tended to substantially reduce both the mean frequency of vomits and the number of shrews vomiting during the early-phase, these reductions failed to attain significance. When combined with a first (tropisetron)- or a second (palonosetron)-generation 5-HT 3 receptor antagonist, pranlukast potentiated their antiemetic efficacy during both phases of vomiting. In addition, pranlukast by itself prevented several intracellular signal markers of cisplatin-evoked delayed-vomiting such as phosphorylation of ERK1/2 and PKA. When pranlukast was combined with either palonosetron or tropisetron, these combinations suppressed the evoked phosphorylation of: i) ERK1/2 during both acute- and delayed-phase, ii) PKCα/β at the peak acute-phase, and iii) PKA at the peak delayed-phase. The current and our published findings suggest that overall behavioral and intracellular signaling effects of pranlukast via blockade of CysLT1 receptors generally appear to be similar to the NK 1 receptor antagonist netupitant with some differences. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00142999
Volume :
809
Database :
Academic Search Index
Journal :
European Journal of Pharmacology
Publication Type :
Academic Journal
Accession number :
123658154
Full Text :
https://doi.org/10.1016/j.ejphar.2017.05.014