Prünte C, Nuttli I, Markstein R, Kohler C
University Eye Clinic, Basel, Switzerland.
J Neural Transm (Vienna). 1997;104(2-3):111-23. doi: 10.1007/BF01273174.
This investigation was designed as a randomized, placebo-controlled, double-masked, crossover study in NZW rabbits with normal intraocular pressure (IOP) to investigate dopaminergic effects on IOP. SKF 38393, a selective D1-receptor agonist, increased, and SDZ PSD-958, a selective D1-receptor antagonist, decreased IOP, respectively. The selective D2-receptor agonist quinpirole decreased IOP, whereas the selective D2 receptor antagonist metoclopramide had no significant effect. Combinations of quinpirole with SDZ PSD-958 decreased IOP in an additive manner. SDZ GLC-756, a mixed D1-receptor antagonist/D2-receptor agonist, decreased IOP in a dose-dependent manner with a maximum effect greater than the maximum effects produced either by the D1-receptor antagonist SDZ PSD-958 and the D2-receptor agonist quinpirole. The effect of SDZ GLC-756 could only be partially blocked by the selective D2-receptor antagonist metoclopramide suggesting that both D1-receptor blockade and D2-receptor stimulation participate in its IOP-lowering effect. Tonography suggests that SDZ GLC-756 has no significant effect on outflow facility. Furthermore, the results suggest that both D1 and D2 receptors each play an independent role in the regulation of IOP in rabbits. Thus, simultaneous blockade of D1 receptors and stimulation of D2 receptors may provide a new pharmacological approach for the treatment of ocular hypertension frequently associated with glaucoma.
本研究设计为一项在正常眼压（IOP）的新西兰白兔中进行的随机、安慰剂对照、双盲、交叉研究，以调查多巴胺能对眼压的影响。选择性D1受体激动剂SKF 38393可升高眼压，而选择性D1受体拮抗剂SDZ PSD - 958可降低眼压。选择性D2受体激动剂喹吡罗可降低眼压，而选择性D2受体拮抗剂甲氧氯普胺则无显著作用。喹吡罗与SDZ PSD - 958联合使用可呈相加作用降低眼压。混合性D1受体拮抗剂/D2受体激动剂SDZ GLC - 756可呈剂量依赖性降低眼压，其最大效应大于D1受体拮抗剂SDZ PSD - 958和D2受体激动剂喹吡罗单独产生的最大效应。选择性D2受体拮抗剂甲氧氯普胺只能部分阻断SDZ GLC - 756的作用，这表明D1受体阻断和D2受体刺激均参与其降低眼压的效应。眼压描记法表明SDZ GLC - 756对房水流畅度无显著影响。此外，结果表明D1和D2受体在兔眼压调节中均发挥独立作用。因此，同时阻断D1受体和刺激D2受体可能为治疗常与青光眼相关的高眼压症提供一种新的药理学方法。
