Ch. Chiang et al., INTRAOCULAR-PRESSURE LOWERING EFFECTS OF NOVEL ARYLPIPERAZINE DERIVATIVES, Journal of ocular pharmacology and therapeutics, 14(4), 1998, pp. 313-322
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.