Intraocular pressure lowering effects of novel arylpiperazine derivatives

Arylpiperazine derivatives were synthesized and investigated in this study. Two animal models, including an intraocular pressure (IOP) recovery method and an alpha-chymotrypsin-induced glaucoma model, were used to determine the ocular pharmacological effects of the arylpiperazine derivatives. In the IOP recovery method, New Zealand rabbits with normal IOP were instilled with 50 microliters of 0.5% eye drops, then 10% sodium chloride solution was infused through the ear marginal vein. The relative percent of IOPs were calculated, then delta IOPt% was obtained from the difference of IOPt% between the treated and controlled eye. In the alpha-chymotrypsin-induced glaucoma model, the induced glaucoma rabbits were topically instilled with 0.5% arylpiperazines onto the eyes, and then the IOP changes were calculated to evaluate the effect of eye drops. Our results showed that in the IOP recovery method, BG31 and YCT2-2 demonstrated a very significant effect for reducing IOP; delta IOPt% were -27.6 and -25.5 for BG31 and YCT2-2, respectively. Two other compounds, C219 and C220 also lowered IOP, but the effects were less significant. In alpha-chymotrypsin-induced glaucoma, the maximum effect of YCT2-2 on the IOP was found at 5 hrs. The delta IOP and delta delta IOP were -12.5 +/- 1.7 and -5.8 +/- 1.1 mmHg (p < 0.01), respectively. For BG-31 and C220, there existed a trend to increase IOP with time. In the study, we found that YCT2-2 with higher solubility in the acidic condition was correlated to the significant IOP lowering effect.