Purpose: To investigate the intraocular pressure (IOP)-reducing effect and side effects of SDZ GLC-756, a novel dopamine D-1 antagonist and D-2 agonist, in control subjects and patients with open-angle glaucoma or ocular hypertension. Methods: A single-application, randomized, placebo-controlled, double-masked study was performed. SDZ GLC-756 eye drops at a concentration of 0.01 % (n = 6) or 0.1% (n = 6) were administered to one eye in control subjects, vehicle alone (control) to the contralateral eye. In glaucoma patients the trial was designed as a crossover study administering SDZ GLC-756 (0.1 %) eye drops and vehicle alone (control) to one eye in 12 patients with open-angle glaucoma or ocular hypertension. Results: In control subjects, IOP decreased significantly by 2.0 ± 0.4 mmHg (P < 0.01) after treatment with 0.01% SDZ GLC-756 and by 4.7 ± 0.5 mmHg (P < 0.001) after treatment with 0.1% SDZ GLC-756. In the glaucoma group, IOP decreased by 6.8 ± 0.6 mmHg (P < 0.001) (range, 4-11 mmHg). In both groups, treatment with 0.1 eye drops resulted in a significant IOP-lowering effect for 6 hours, and for 3 hours with treatment with 0.01 % eye drops. A significant IOP-lowering effect (P < 0.05) also was found in the contralateral eye. Except for slight conjunctival hyperemia lasting up to 30 minutes after drug application, no ocular or systemic side effects were observed. Conclusion: SDZ GLC-756 reduced IOP significantly for approximately 6 hours. However, due to the study design with repeated IOP measurements before drug administration, the clinical efficacy of the preparation used remains unclear. The only systemic or local side effect observed was slight conjunctival hyperemia. The simultaneous D-1 antagonistic and D-2 agonistic properties of SDZ GLC-756 may provide a new pharmacologic approach to treating glaucoma and ocular hypertension, which deserves further investigation.