Chapter 5 Central Nervous Stimulant And Diuretics

5.1 central nervous stimulants 中枢兴奋药是提高中枢神经系统功能的药 物，对呼吸中枢有较明显的选择作用。用于 抢救各种危重疾病及中枢抑制药中毒引起的 呼吸抑制。 Central stimulant is the drug to improve the function of the central nervous system. It has more selective to respiratory center and is used for emergency treatment of critical diseases and respiratory center inhibition poisoning caused by central inhibitors.

5.1.1 Alkaloids

Central nervous stimulating: caffeine>theobromine>theophylline Heart stimulating and bronchial smooth muscle relaxation: theophylline>theobromine>caffeine

5.1.2 Amides Nikethamide and piracetam

5.1.3 other konds else Meclofenoxate hydrochloride

5.2 Diuretics 按效能分为三类 高效能利尿药：髓袢升支粗段髓质部和皮质部 中效能利尿药：髓袢升支粗段皮质部，远曲小管前段 低效能利尿药：近曲小管，远曲小管后段，皮质集合管 Divided into three categories according to performance: High-performance diuretics Medium-performance diuretics Low performance diuretics

5.2.1 The discovery and development of diuretics

5.2.2 Sulfa diuretics ----Carbonic anhydrase inhibitors 碳酸酐酶体内将二氧化碳和水合成碳酸，碳酸解离出的氢离 子在肾小管与钠离子交换促进钠离子重吸收，当碳酸酐酶作 用被抑制后，碳酸的形成减少，使得肾小管内可与钠离子交 换的氢离子减少，增加钠离子的排出量。 Carbon dioxide and water can be synthesized into carbonic acid by carbonic anhydrase in vivo. Carbonic acid ionize hydrogen ion and the hydrogen ions exchange with sodium ions in renal tubular to promote the re-absorption of sodium, when the role of carbonic anhydrase was inhibited, the production of carbonic acid is reduced so that there are not enogh hydrogen ions to exchange with sodium ions,as a result, an increase of sodium ion emissions.

Acetazolamide is the representative of sulfa diuretics. acetazolamide can reduce the production of water in eye of glaucoma patients,so can reduce intraocular pressure, mainly used in clinical treatment of glaucoma.

5.2.3 噻嗪类 thiazides Hydrochlorothiazide Chemical Name: 6 - chloro -3,4 - dihydro-2H-1, 2,4 - benzothiadiazines -7 - sulfonamide -1,1 - dioxide Properties: soluble in alkaline aqueous solution, solid stability, and aqueous solution hydrolysis Metabolism: main excretion from renal tubular by means of prototype,little by liver metabolism, Applications: chronic heart failure, essential hypertension, diabetes insipidus, high Ca

Synthesis and SAR 可用酮基代替 被烷基取代延 长作用时间 引入亲脂性取 代基增加活性 无双键较有双 键活性高 引入吸电子基活性 更高，尤以氯或三 氟甲基活性最高。 推电子基如甲氧基 等使活性降低 除去或被其他集团 取代失去利尿活性

5.2.4 其它类 螺内酯 spironolactone

Metabolism: 70% of the drug is absorbed immediately after oral action, in the liver can easily be metabolized to generate canrenone and canrenone acid. Mechanism: pure antagonist to mineralocorticoid, inhibition to reabsorption of potassium and sodium. Disadvantage: The main side effects of hyperkalemia, anti-androgen effect

氨苯蝶啶 Triamterene Pteridine Chemical name: 2,4,7 - triamino -6 - phenyl Pteridine Properties: odorless, tasteless, slightly soluble in water Mechanisms: impact the cation exchange at distal convoluted tubule, blocking Na + reabsorption and K + excretion, but also have side-effects of hyperkalemia.

呋塞米 furosemide Chemical Name: 2 - [(2 - furylmethyl) amino] -5 - (ammonia sulfonyl) -4 - chlorobenzoic acid Properties: aqueous sodium solution, produce green precipitate with CuSO4 Alcohol solution give red solution with dimethylamino-benzaldehyde. Mechanisms: belong to Sulfonamide diuretics, inhibit renal carbonic anhydrase activity, cause increasing emission of Na +, HCO3-and H2O. Metabolism: mainly excretion by prototype. Applications: acute left heart failure, pulmonary edema, cerebral edema, hypertension and chronic renal insufficiency.

synthesis