Red-emissive fluorescent probes have been developed by integration of quinoline blue or thiazole red as the base surrogate into triplex-forming PNAs, allowing selective sensing of a sequence of double-stranded RNA.

The inhibitory effects of sodium 3-guanidinocarbonyl-2-methyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-9-ylmethyl sulfate monoethanolate (TY-51924) are selective for Na(+)/H(+) exchanger (NHE)-1 in PS120 cells expressing human NHE isoforms assayed by NH(4)Cl prepulse technique. The median inhibitory concentrations (micromolar) of TY-51924 were 0.095 ± 0.008 (NHE-1), 0.621 ± 0.093 (NHE-2), and >100 (NHE-3). In anesthetized dogs subjected to 90 minutes ischemia/300 minutes reperfusion, intravenous bolus TY-51924 at 5 and 10 mg/kg administered 5 minutes before reperfusion reduced infarct size. The infarct size reduction ratios of TY-51924 at 5 and 10 mg/kg versus vehicle were 32.8% and 52.4%, respectively. But TY-51924 at 10 mg/kg administered 10 minutes after reperfusion did not reduce infarct size. In 2-step intravenous infusion initiated 15 minutes before reperfusion, TY-51924 at low dose (3.8 mg/kg per 5 minutes, then 6.2 mg/kg per 20 minutes) and at high dose (7.6 mg/kg per 5 minutes, then 12.4 mg/kg per 20 minutes) reduced infarct size. The infarct size reduction ratios of TY-51924 at 10 and 20 mg/kg versus vehicle were 39.2% and 51.7%, respectively; plasma drug concentrations at reperfusion were 16.8 and 38.8 μg/mL, respectively. This indicates that maintaining a plasma drug concentration of >20 μg/mL at reperfusion enables TY-51924 to reduce infarct size by inhibiting the NHE, which is activated during the early period of reperfusion.

These results suggest that the synthetic cannabinoid CP55940 negatively modulates cytokine mRNA expression in cerebellar granule cells by a CB and GPR55 receptor-independent mechanism.