CANNABINOIDS AS ANTIHYPERTENSIVE AGENTS

H.G.Pars药物实验室的长期目标是开发和 销售一种口服活性降压药，来自其系列硫磺和 氮类大麻类似物。 据信，低血压的大麻素类药物通过改变 但中枢交感神经系统活动的确切机制 作用尚不清楚，可能与降压药不同 市场。 初步的心血管/行为数据表明，有四个帕金森病患者 化合物(SP-119、SP-269、273和276)表现出良好的分离效果。 降压活性和不良反应。低血压 清醒和麻醉自发性高血压(SH)和 血压正常的大鼠持续时间长，大小与之相当 可乐定。 在第一阶段，我们将重新合成四个类似物并执行更多操作 对其在SH大鼠和大鼠体内抗高血压活性的广泛评价 对小鼠的行为影响。拥有最佳治疗比例的候选人， SP-X将在20天的重复剂量研究中进行进一步评估。 结果将与可乐定数据进行比较。 成功完成该项目将允许申请第二阶段 用于制备SP-X口服制剂的资金，用于临床前 研究并在人体受试者中进行早期安全性和有效性试验。

H. G. Pars Pharmaceutical Laboratories' long-term goal is to develop and market an orally active antihypertensive drug from its series of sulfur and nitrogen cannabinoid analogs. Hypotensive cannabinoids are believed to exert their effects by altering central sympathetic nervous system activity but the exact mechanism of action is not known and may differ from that of antihypertensive agents on the market. Preliminary cardiovascular/behavioral data indicates that four PARS' compounds (SP-119, SP-269, 273 and 276) show a favorable separation of blood pressure lowering activity and adverse side effects. Hypotensive activity in conscious and anesthetized spontaneous hypertensive (SH) and normotensive rats was of long duration and comparable in magnitude to that of Clonidine. During Phase I we will resynthesize the four analogs and perform more extensive evaluations of their antihypertensive activity in SH rats and behavorial effects in mice. The candidate with the best therapeutic ratio, SP-X, will undergo further evaluation in a 20 day repeat dose study. Results will be compared with clonidine data. Successful completion of this project will allow application for Phase II funds for preparing an oral formulation of SP-X, performing pre-clinical studies and conducting early safety and efficacy trials in human subjects.