上海交通大学：《药理学 Pharmacology》课程教学资源（讲义课件）药理学教学教案（二）

Autacoid Drugs ·Autacoids(自体活性物质)are biological factors made in the body that act like"local hormones", have a brief duration,act near the site of synthesis (paracrine),and are not blood borne. Autacoids are regulating molecules metabolized locally. These factors can have many different biological actions. Major autacoids ·Arachidonic acid metabolites(花生四烯酸) including:prostaglandins(前列腺素)， thromboxanes(血栓素)，leukotrienes(白三烯) ·5-hydroxytryptamine,5-HT(五羟色胺)，also named serotonin(血清素) ·Bradykinin(缓激肽) ·Endothelin(内皮素) Substance P(P物质)

Autacoid Drugs • Autacoids (自体活性物质) are biological factors made in the body that act like “local hormones”, have a brief duration, act near the site of synthesis (paracrine), and are not blood borne. • Autacoids are regulating molecules metabolized locally. • These factors can have many different biological actions. Major autacoids • Arachidonic acid metabolites (花生四烯酸) including：prostaglandins (前列腺素), thromboxanes (血栓素), leukotrienes (白三烯) • 5-hydroxytryptamine, 5-HT (五羟色胺）,also named serotonin (血清素) • Bradykinin (缓激肽) • Endothelin (内皮素) • Substance P (P 物质)

Synthesis of Eicosanoids(二十烷类) 777777 4… Phospholipase Ae Arachidonic acid 5-Lpox闪ygenase Prostaglandin G2 5-HPETE Prostaglandin H2 Leukotriene A Prostaglandin l2 Prosta Prostaglandin F2o Leukotriene Da Leukotriene E Arachidonic Acid (AA) (5.8.11.14 eicosatetraenoic acid) COOH 入CH3 .20 carbon,unsaturated fatty acid .Gives rise to PGs,thromboxanes and leukotrienes .Phospholipase A2(PLA2)and phospholipase C(PLC)generate AA from phospholipids and diacylglycerols .Fatty acid cyclooxygenases(COX-1 and COX-2)initiate the biosynthesis of the PGs and TXs(prostanoids) .Various lipoxygenases give rise to leukotrienes and lipoxins (inhib.of lipoxygenase are potential anti-asthmatic drugs)

Synthesis of Eicosanoids (二十烷类)

977779 4688 Phospholipase A2+ Injury or other stimulus Arachidonic acid Cyclooxygenase 5-Lipoxygenase (COX) Prostaglandin G2 5-HPETE Prostaglandin H2 Leukotriene A4 Prostaglandin 12 Prostaglandin E2 Thromboxane A2 Leukotriene B4 Leukotriene Ca Prostaglandin F2 Leukotriene D4 Leukotriene E 贝前列素Beraprost Beraprost is a synthetic analogue of prostacyclin.under clinical trials for the treatment of pulmonary hypertension.It is also being studied for use in avoiding reperfusion injury. As an analogue of prostacyclin PG12,beraprost effects vasodilation,which in turn lowers the blood pressure.Beraprost also inhibits platelet aggregation,though the role this phenomenon may play in relation to pulmonary hypertension has yet to be determined

贝前列素 Beraprost As an analogue of prostacyclin PGI2, beraprost effects vasodilation, which in turn lowers the blood pressure. Beraprost also inhibits platelet aggregation, though the role this phenomenon may play in relation to pulmonary hypertension has yet to be determined. Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the treatment of pulmonary hypertension. It is also being studied for use in avoiding reperfusion injury

前列地尔Alprostadil Prostaglandin E1 (PGE1),known pharmaceutically as alprostadil,is a prostaglandin.It is a drug used in the treatment of erectile dysfunction[2]and has vasodilatory properties. 依前列醇Epoprostenol Prostacyclin(or PGI2),as a drug,is known as 'epoprostenol".The terms are sometimes used interchangeably. Prostacyclin(PGI2)chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation).It does this by inhibiting platelet activation.It is also an effective vasodilator.Prostacyclin's interactions in contrast to thromboxane(TXA2),another eicosanoid,strongly suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage

前列地尔 Alprostadil Prostaglandin E1 (PGE1), known pharmaceutically as alprostadil, is a prostaglandin. It is a drug used in the treatment of erectile dysfunction[2] and has vasodilatory properties. 依前列醇 Epoprostenol Prostacyclin (or PGI2), as a drug, is known as "epoprostenol". The terms are sometimes used interchangeably. Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It does this by inhibiting platelet activation. It is also an effective vasodilator. Prostacyclin's interactions in contrast to thromboxane (TXA2), another eicosanoid, strongly suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage

米索前列醇Misoprostol HO Pharmacologically,misoprostol is a synthetic prostaglandin E1(PGE1)analogue. Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug (NSAID)induced gastric ulcers,for early abortion,to treat missed miscarriage,and to induce labor.The latter use is controversial in the United States.Misoprostol was invented and marketed by G.D.Searle Company (now Pfizer)under the trade name Cytotec. 地诺前列酮Dinoprostone,PGE2 OH HO OH The naturally occurring prostaglandin E2(PGE2)is known in medicine as dinoprostone.It has important effects in labor(softens cervix and causes uterine contraction)and also stimulates osteoblasts to release factors that stimulate bone resorption by osteoclasts.PGE2 is also the prostaglandin that ultimately induces fever

米索前列醇 Misoprostol Pharmacologically, misoprostol is a synthetic prostaglandin E1 (PGE1) analogue. Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug (NSAID) induced gastric ulcers, for early abortion, to treat missed miscarriage, and to induce labor. The latter use is controversial in the United States. Misoprostol was invented and marketed by G.D. Searle & Company (now Pfizer) under the trade name Cytotec. 地诺前列酮 Dinoprostone, PGE2 The naturally occurring prostaglandin E2 (PGE2) is known in medicine as dinoprostone. It has important effects in labor (softens cervix and causes uterine contraction) and also stimulates osteoblasts to release factors that stimulate bone resorption by osteoclasts. PGE2 is also the prostaglandin that ultimately induces fever

卡前列素Carboprost,PGF2a HQ HO Carboprost is a synthetic prostaglandin analogue of PGF2 a (specifically,it is 15- methyl-PGF2 a)with oxytocic properties. Carboprost induces contractions and can trigger abortion in early pregnancy.It also reduces postpartum bleeding. Synthesis and inhibition of leukotrienes Leukcyte LTE LTD Leukocytes PLA Zleuton S9g→tca 5-poxygenase acid Gi-LCAMP BLT, Inhibition at the 5-LOX level and at the receptor level

卡前列素 Carboprost, PGF2α Carboprost is a synthetic prostaglandin analogue of PGF2α (specifically, it is 15- methyl-PGF2α) with oxytocic properties. Carboprost induces contractions and can trigger abortion in early pregnancy. It also reduces postpartum bleeding. Synthesis and inhibition of leukotrienes Inhibition at the 5-LOX level and at the receptor level

扎鲁司特Zafirlukast 孟鲁司特Montelukast (Singulair) Montelukast is a CysLT1 antagonist;that it blocks the action of leukotriene D4 (and secondary ligands LTC4 and LTE4)on the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes by binding to it.This reduces the bronchoconstriction otherwise caused by the leukotriene and results in less inflammation. 齐留通Zileuton NH2 5-lipoxygenase inhibitor Zileuton(introduced in 1996 by Abbott Laboratories)is an active oral inhibitor of the enzyme 5-lipoxygenase,which forms leukotrienes from arachidonic acid.Zileuton is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. Zileuton is not indicated for use in the reversal of bronchospasm in acute asthma attacks.Therapy with zileuton can be continued during acute exacerbations of asthma

扎鲁司特 Zafirlukast 孟鲁司特 Montelukast (Singulair) Montelukast is a CysLT1 antagonist; that it blocks the action of leukotriene D4 (and secondary ligands LTC4 and LTE4) on the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction otherwise caused by the leukotriene and results in less inflammation. 齐留通 Zileuton Zileuton (introduced in 1996 by Abbott Laboratories) is an active oral inhibitor of the enzyme 5-lipoxygenase, which forms leukotrienes from arachidonic acid. Zileuton is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. Zileuton is not indicated for use in the reversal of bronchospasm in acute asthma attacks. Therapy with zileuton can be continued during acute exacerbations of asthma. 5-lipoxygenase inhibitor

5-羟色胺5-hydroxytryptamine,5-HT Serotonin(血清素) HO 5-HT)is a monoamine neurotransmitter.Biochemically derived from tryptophan,serotonin is primarily found in the gastrointestinal(Gl)tract, platelets,and in the central nervous system(CNS)of animals including humans.It is a well-known contributor to feelings of well-being:it is also known to contribute to happiness. 舒马普坦Sumatriptan 5-HT1B and 5-HT1D agonist Sumatriptan is a triptan sulfa drug containing a sulfonamide group.It is used for the treatment of migraine headaches.Sumatriptan is produced and marketed by various drug manufacturers with many different trade names such as Sumatriptan,Imitrex,Imigran,Imigran recovery.Sumatriptan is structurally similar to serotonin(5HT),and is a 5-HT(types 5-HT1D and 5-HT1B)agonist. The specific receptor subtypes it activates are present on the cranial arteries and veins.Acting as an agonist at these receptors,Sumatriptan reduces the vascular inflammation associated with migraine

5-羟色胺 5-hydroxytryptamine, 5-HT Serotonin (血清素) 5-HT) is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS) of animals including humans. It is a well-known contributor to feelings of well-being; it is also known to contribute to happiness. 舒马普坦 Sumatriptan Sumatriptan is a triptan sulfa drug containing a sulfonamide group. It is used for the treatment of migraine headaches. Sumatriptan is produced and marketed by various drug manufacturers with many different trade names such as Sumatriptan, Imitrex, Imigran, Imigran recovery. Sumatriptan is structurally similar to serotonin (5HT), and is a 5-HT (types 5-HT1D and 5-HT1B) agonist. The specific receptor subtypes it activates are present on the cranial arteries and veins. Acting as an agonist at these receptors, Sumatriptan reduces the vascular inflammation associated with migraine. 5-HT1B and 5-HT1D agonist

丁螺环酮Buspirone 依沙匹隆Ipsapirone Buspirone(trade name Buspar)is an anxiolytic psychoactive drug of the azapirone chemical class,and is primarily used to treat generalized anxiety disorder(GAD). Ipsapirone is a selective 5-HT1A receptor partial agonist of the piperazine and azapirone chemical classes.It has antidepressant and anxiolytic effects 芬氟拉明Fenfluramine Fenfluramine(3-trifluoromethyl-N-ethylamphetamine.trade names Pondimin,Ponderax and Adifax)is a drug that was part of the Fen-Phen anti-obesity medication(the other drug being phentermine).Fenfluramine was introduced on the U.S.market in 1973.It is the racemic mixture of two enantiomers,dextrofenfluramine and levofenfluramine.It increases the level of the neurotransmitter serotonin,a chemical that regulates mood,appetite and other functions.Fenfluramine causes the release of serotonin by disrupting vesicular storage of the neurotransmitter,and reversing serotonin transporter function.The end result is a feeling of fullness and loss of appetite

丁螺环酮 Buspirone 依沙匹隆 Ipsapirone Buspirone (trade name Buspar) is an anxiolytic psychoactive drug of the azapirone chemical class, and is primarily used to treat generalized anxiety disorder (GAD). Ipsapirone is a selective 5-HT1A receptor partial agonist of the piperazine and azapirone chemical classes. It has antidepressant and anxiolytic effects 芬氟拉明 Fenfluramine Fenfluramine (3-trifluoromethyl-N-ethylamphetamine, trade names Pondimin, Ponderax and Adifax) is a drug that was part of the Fen-Phen anti-obesity medication (the other drug being phentermine). Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine. It increases the level of the neurotransmitter serotonin, a chemical that regulates mood, appetite and other functions. Fenfluramine causes the release of serotonin by disrupting vesicular storage of the neurotransmitter, and reversing serotonin transporter function. The end result is a feeling of fullness and loss of appetite

赛庚啶Cyproheptadine Selective 5-HT2 blocker Cyproheptadine(trade name Periactin)is an antihistaminic/anticholinergic and antiserotonergic agent.It also acts as a 5-HT2 receptor antagonist as well as blocking calcium channels.Cyproheptadine has shown effectiveness in the treatment of nightmares including nightmares related to post traumatic stress disorder Polypeptide drugs 缓激肽Bradykinin Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins,consisting of nine amino acids.Bradykinin is a peptide that causes blood vessels to dilate(enlarge),and therefore causes blood pressure to lower.A class of drugs called ACE inhibitors,which are used to lower blood pressure,increase bradykinin(by inhibiting its degradation)further lowering blood pressure.Bradykinin works on blood vessels through the release of prostacyclin,nitric oxide,and endothelium- derived hyperpolarizing factor

赛庚啶 Cyproheptadine Cyproheptadine (trade name Periactin) is an antihistaminic/anticholinergic and antiserotonergic agent. It also acts as a 5-HT2 receptor antagonist as well as blocking calcium channels. Cyproheptadine has shown effectiveness in the treatment of nightmares including nightmares related to post traumatic stress disorder Selective 5-HT2 blocker 缓激肽 Bradykinin Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg Polypeptide drugs Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids. Bradykinin is a peptide that causes blood vessels to dilate (enlarge), and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin (by inhibiting its degradation) further lowering blood pressure. Bradykinin works on blood vessels through the release of prostacyclin, nitric oxide, and endothelium￾derived hyperpolarizing factor