Obesity Drugs Group： 林雨 华峥 俞爽 竺芳欢 杜岩松 刘嘉越余梓仪 都津铭 田煜琦.

Presentation on theme: "Obesity Drugs Group： 林雨 华峥 俞爽 竺芳欢 杜岩松 刘嘉越余梓仪 都津铭 田煜琦."— Presentation transcript:

1 Obesity Drugs Group： 林雨 华峥 俞爽 竺芳欢 杜岩松 刘嘉越余梓仪 都津铭 田煜琦

2 Obesity Definition： Risk BMI ≥ 30kg/m2
Part 1 Definition： BMI ≥ 30kg/m2 Risk Dyslipidaemia, hypertension, stroke, myocardial infarction, Type 2 diabetes and some cancers Part 2 Part 3 Part 4 Part 5

3 Digestion Orlistat 奥利司他 Part 1 Part 2 Part 3
Inhibitor of gastric and pancreatic lipases that blocks fat absorption from the gut Part 4 对脂肪的难以吸收导致了对肠道的不良反应，如油便、脂肪便、肠胃气胀、脱粪等等，但这些不良反应可以通过降低膳食中的脂肪含量来减弱。 在减少脂肪吸收的同时，也减少了脂溶性维生素(维生素 A／D／E ) 、矿物元素(钙和钾)及某些药物的吸收 会引起严重肝损伤、急性胰腺炎、急性肾损伤和结肠癌癌前病变。 Part 5

4 Digestion Cetilistat 西替利斯它 A newer inhibitor of gastric and pancreatic
Part 1 Part 2 Cetilistat 西替利斯它 A newer inhibitor of gastric and pancreatic Fewer adverse side-effects than orlistat Part 3 Part 4 Part 5

5 Mechanism／Effects Part 1 Centrally-acting Part 2 Part 3 Part 4 Part 5

6 Regulation of central nervous system

7 CRH CART Orexin MCH Cannabinoid & 5-HT systems AgRP GABA

8 Metreleptin 美曲普汀 Recombinant human methl leptin 第一个问世的瘦素类药物 🙂弥补瘦素缺乏，抑制脂肪代谢障碍 🙃不良反应：恶心、呕吐、血糖下降、淋巴结异常等 💊2014

9 Cannabinoid Rimonabant 利莫那班 CB-1 receptor antagonist
Serum endocannabinoid levels are elevated in obesity ——CB1 activation in weight gain CB-1 receptor antagonist 🙂Very effective in promoting weight loss 🙃Mood-related disorders 😭Withdrawn from the market

10 5-HT system ⬇️GABAergic inhibitory input to POMC cells
5-HT1B receptors NPY/Agrp neurons⬇️ POMC and NPY neurons 5-HT2C receptors

11 5-HT system Sibutramine 西布曲明 Dexfenlfuramine 右芬弗拉明
Centrally-acting noradrenaline/serotonin reuptake inhibitor 🙃Increase in non-fatal heart attacks and strokes in subjects with preexisting cardiovascular problems 😭Withdrawn from the market 5-HT receptor agonist 🙃Life-threatening primary pulmonary hypertension and cardiac valvulopathy 😭Withdrawn from the market

12 Lorcaserin 氯卡色林 Selective 5-HT2C receptor agonist 🙂Avoid heart valve damage 🙃Blurred vision, dizziness, somnolence, headache, gastrointestinal disturbance and nausea 💊2012

13 Topiramate 托吡酯 GABA

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15 Amylin 胰淀素（胰淀粉样多肽类似物）
Pramlintide 普兰林肽 Amylin A stable, soluble, equipotent amylin analog Administered by mealtime subcutaneous injection. Diabetes treatment Glucose-dependent 💊On the way Amylin 胰淀素（胰淀粉样多肽类似物） Stored in pancreatic b-cells Co-secreted with insulin postprandially Vagus-independent actions on the hindbrain area postrema Inhibiting gastric emptying, gastric acid output, and glucagon secretion.

16 Contrave （Bupropion/Naltrexone）
Opioid receptor related Contrave （Bupropion/Naltrexone） 💊2014 Nahrexone 纳曲酮 Non-selective opioid receptor antagonist To treat opiate and alcohol dependence syndromes Bupropion 安非他酮 A weak, selective dopamine reuptake inhibitor To treat depression An aid to smoking cessation

17 Liraglutide 利拉鲁肽 Beloranib Glucagon-like peptide-1 (GlP-1) 💊2014
Others Liraglutide 利拉鲁肽 Glucagon-like peptide-1 (GlP-1) 💊2014 Beloranib MetAP inhibitor —— 抑制饥饿感 增加脂肪消耗 💊On the way

18 Others Tesofensine 特索芬辛 Potent, non-selective reuptake inhibitor of dopamine, noradrenaline and 5-HT 🙃Dose-dependent increases in diastolic blood pressure and heart rate; Psychiatric adverse events 💊On the way

19 Metabolism （L-carnitine 左旋肉碱）
Part 1 Part 2 （L-carnitine 左旋肉碱） Endogenous molecule involved in fatty acid metabolism Help reduce oxidative stress L-carnitine alone showed to have only a little effect on weight loss and appetite suppression Part 3 Part 4 Part 5

20 Metabolism β3-肾上腺素受体激动剂
Part 1 Part 2 β3-肾上腺素受体激动剂 β3肾上腺素受体激动剂能显著减轻啮齿动物体重，促进白色脂肪组织的脂肪分解，并加强棕色脂肪组织非颤栗性产热作用，降低血糖，也不影响摄食，因此被认为是抗肥胖和抗糖尿病的较理想药物。 Part 3 Part 4 Part 5

21 UCP (Uncoupling protein) 解偶联蛋白
Part 1 Part 2 UCP (Uncoupling protein) 解偶联蛋白 一类线粒体内膜上的载体，可以将H+从线粒体内膜渗透到线粒体基质中，减少ATP的合成并产生热能。 虽然UCP在肥胖发生中所起的作用不是很清楚。但是实验表明，UCP高表达于WAT和BAT中，可使遗传肥胖的小鼠体重下降，并且皮下脂肪减少。 Part 3 Part 4 Part 5

22 Market 奥利司他 (Orlistat)胶囊 氯卡色林 (Lorcaserin)
苯丁胺和托吡酯 (Phentermine/Topiraate)缓释剂胶囊 盐酸安非他酮与盐酸纳曲酮(Bupropion/Naltrexone)复方缓释片 利拉鲁肽(Liraglutide)注射液

23 Thank you