2002 年 21 巻 3-4 号 p. 129-133
GLC756 is an octahydrobenzo-quinoline which has combined dopamine D-1 antagonistic and dopamine D-2 agonistic properties. It may induce both a decrease in aqueous humor formation and an increase in uveoscleral outflow. The purpose of this study was to observe the effects on intraocular pressure (IOP) of topically administered 0.4% GLC756 solution, the duration of action, and any side effects in Rhesus monkeys with laser-induced ocular hypertension.
Ten male monkeys with argon laser-induced ocular hypertension in one eye were sedated with ketamine hydrochloride, and the IOP measured in both eyes at 7:00 am, 7:30 am, and then hourly until 1:00 pm with a TonopenTM XL applanation tonometer (Mentor®, Norwell, MA, U.S.A). During the first week, IOP baselines were obtained. The following week, 0.4% GLC756 solution was administered at 7:00 am in the hypertensive eye and the IOP measurements repeated hourly until 1:00 pm. Baseline and drug response curves, and intraocular pressure time profiles for both eyes in each animal were developed.
The baseline IOP was significantly higher in the experimental hypertensive eye than in the normal eye (29.9±2.7 versus 14.5±0.7 mmHg, p<0.0001). The mean IOP in the lasered eye treated with 0.4% GLC756 at 7:00 am decreased from 7:00 to 9:00 am, and then slightly increased until 1:00 pm. The maximal mean IOP decrease (8.5 mmHg) occurred one hour after application of the drug solution. A significant IOP lowering effect was observed 30 minutes after administration of the solution and remained low for two hours. No ocular (such as itching or pain) or systemic side effects to the medication were observed. The IOP in the control eye varied slightly from 7:00 am to 1:00 pm. GLC756 at a concentration of 0.4% significantly lowers the IOP in Rhesus monkeys with laser-induced ocular hypertension. This differs from previous studies performed in humans and rabbits. The IOP lowering effects are more pronounced, but only for a short period of time, in monkeys when compared to the effects observed in humans and rabbits.
GLC756 could be a useful and well-tolerated ocular hypotensive agent and should be investigated further.
