Tropisetron Hydrochloride (SDZ-ICS-930) is a selective 5-HT3 receptor antagonist and α7-nicotinic receptor agonist with an IC50 of 70.1 ± 0.9 nM for 5-HT3 receptor.IC50 value: 70.1 ± 0.9 nMTarget: 5-HT3 receptor; α7-nicotinic receptorin vitro: Retinal ganglion cells(RGCs) pretreated with 100 nM tropisetron before glutamate increased cell survival to an average of 105% compared to controls. Inhibition studies using the alpha7 nAChR antagonist, MLA (10 nM), support the hypothesis that tropisetron is an effective neuroprotective agent against glutamate-induced excitotoxicity; mediated by α7 nAChR activation. Tropisetron had no discernible effects on pAkt levels but significantly decreased p38 MAPK levels associated with excitotoxicity from an average of 15 ng/ml to 6 ng/ml [2]. Tropisetron, but not granisetron, significantly inhibits the phosphatase activity of calcineurin, over-expresses the CB(1) receptors at both transcriptional and protein levels, and reduces cAMP content in cerebellar granule neurons (CGNs) [4].in vivo: Animals were treated intracerebroventricularly with tropisetron, mCPBG (selective 5-HT3 receptor agonist) or mCPBG plus tropisetron on days 1, 3, 5 and 7. Tropisetron significantly diminished the elevated levels of these markers and reversed the cognitive deficit. Interestingly, tropisetron was also found to be a potent inhibitor of calcineurin phosphatase activity [1]. tropisetron (5mg/kg/day) plus mCPBG (10mg/kg/day), and granisetron (5mg/kg/day) intraperitoneally on days 3-35 post-immunization. Treatment with tropisetron and granisetron markedly suppressed the clinical symptoms of EAE (p<0.001) and reduced leukocyte infiltration as well as demyelination in the spinal cord (p<0.05) [3].
References:
[1]. Rahimian R, et al. Tropisetron attenuates amyloid-beta-induced inflammatory and apoptotic responses in rats. Eur J Clin Invest. 2013 Oct;43(10):1039-51.
[2]. Swartz MM, et al. Tropisetron as a neuroprotective agent against glutamate-induced excitotoxicity and mechanisms of action. Neuropharmacology. 2013 Oct;73:111-21.
[3]. Aminian A, et al. Tropisetron diminishes demyelination and disease severity in an animal model of multiple sclerosis. Neuroscience. 2013 Jun 15;248C:299-306.
[4]. Rahimian R, et al. Tropisetron upregulates cannabinoid CB1 receptors in cerebellar granule cells: possible involvement of calcineurin. Brain Res. 2011 Oct 12;1417:1-8.