INTRAOCULAR-PRESSURE LOWERING EFFECTS OF NOVEL ARYLPIPERAZINE DERIVATIVES

Arylpiperazine derivatives were synthesized and investigated in this s tudy. Two animal models, including an intraocular pressure (IOP) recov ery 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 nor mal IOP were instilled with 50 mu l of 0.5% eye drops, then 10% sodium chloride solution was infused through the ear marginal vein. The rela tive percent of IOPs were calculated, then Delta IOPt% was obtained fr om the difference of IOPt% between the treated and controlled eye. In the alpha-chymotrypsin-induced glaucoma model, the induced glaucoma ra bbits were topically instilled with 0.5% arylpiperazines onto the eyes , and then the IOP changes were calculated to evaluate the effect of e ye 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 oth er compounds, C219 and C220 also lowered IOP, but the effects were les s significant. In alpha-chymotrypsin-induced glaucoma, the maximum eff ect of YCT2-2 on the IOP was found at 5 hrs. The Delta IOP and Delta D elta 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. I n the study, we found that YCT2-2 with higher solubility in the acidic condition was correlated to the significant IOP lowering effect.