Buchwald A, Browne C E, Wu W M, Ji F, Bodor N
Center for Drug Discovery, College of Pharmacy, University of Florida, Gainesville, USA.
Pharmazie. 2000 Mar;55(3):196-201.
Cannabinoids have intraocular pressure (IOP) lowering effects, thus, they have a therapeutic potential in the treatment of glaucoma. Unfortunately, in the same time, they show CNS and cardiovascular effects as well. Our aim was to develop a safer, cannabinoid type anti-glaucoma agent, a topically applied soft analogue, that has local, but no systemic effect. The lead compound chosen was a nitrogen-containing cannabinoid analogue that was shown to have IOP lowering activity. A full library of possible soft drugs was generated and the structures were ranked based on the closeness of calculated properties to those of the lead compound. The lead compound has been synthesized, and a preliminary pharmacological study was performed. The structure-activity relationship and pharmacological results indicate a good possibility for the development of a safe, soft anti-glaucoma agent.
大麻素具有降低眼压（IOP）的作用，因此，它们在青光眼治疗中具有治疗潜力。不幸的是，与此同时，它们也表现出中枢神经系统和心血管方面的作用。我们的目标是开发一种更安全的大麻素类抗青光眼药物，一种局部应用的软类似物，它具有局部作用但无全身作用。所选的先导化合物是一种含氮大麻素类似物，已证明其具有降低眼压的活性。生成了一个完整的可能的软药库，并根据计算性质与先导化合物性质的接近程度对结构进行了排序。已合成了先导化合物，并进行了初步的药理学研究。构效关系和药理学结果表明开发一种安全的软抗青光眼药物具有很大可能性。
