Drugs affecting autacoids

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Presentation transcript:

Drugs affecting autacoids

Autacoids: local hormones A. Overview Autacoids: local hormones one of the regulatory mechanisms in the body

neurohormone secretion neurotrasmitter hormone secretion neurohormone secretion

gap junction paracrine 旁分泌 autocrine 自分泌 juxtacrine接触分泌

A. Overview Autacoids: Histamine 5-Hydroxytryptamine (serotonin, 5-HT) Lipid-derived autocoids Prostaglandins (PGs) Leukotrienes (LTs) Platelet activating factor (PAF) Vasoactive peptides Substance P (SP)；Kinins (bradykinin, etc.) Angiotensins (AT)；Natriuretic peptides (NP) Vasoactive intestinal peptide (VIP) Endothelins (ET) Calcitonin gene related peptide (CGRP) Nitric oxide (NO) Adenosine

Lipid-derived autacoids and related drugs PAF Lipid-derived autacoids and related drugs antagonists inhibitors antagonists

Prostaglandins (PGs)

Leukotrienes (LTs): LTB4; LTC4, LTD4, LTE4

B. Histamine receptor antagonists H1 receptor agonists: Histamine(组胺) 2-methyl histamine(2-甲基组胺) Betahistine (培他司汀) H2 receptor agonists: Betazole (培他唑) Impromidine(英普咪定) H3 receptor agonists: R()-methylhistamine(R ()-甲基组胺)

3 principal physiological effects: (1) it is a mediator of inflammation (swelling) associated with the immune response (2) it is a chemical that stimulates secretion of gastric acid (3) it is a transmitter amine in both the peripheral and the central nervous systems.

B. Histamine receptor antagonists

Pioneers in the discovery of histamine and the development of histamine antagonist drug research Clin Pharmacol Drug Dev. 2016 Jan;5(1):5-12. doi: 10.1002/cpdd.236. Review

B. Histamine receptor antagonists First Generation agents 苯海拉明氯苯那敏（扑尔敏） Clin Pharmacol Drug Dev. 2016 Jan;5(1):5-12. doi: 10.1002/cpdd.236. Review

B. Histamine receptor antagonists 1. Pharmacological effects (1) Inhibition of allergic inflammation: mainly on microvascular leakage (2) Central depression: diphenhydramine, promethazine (异丙嗪) > chlorpheniramine > astemzole (阿司咪唑，息斯敏)，phenindamine (苯茚胺)：stimulating (3) Antiemesis: motion sickness (4) Others: weak muscarinic block, local anesthetic, and quinidine-like effects

B. Histamine receptor antagonists 2. Clinical uses (1) Allergic conditions: symptoms in skin and mucosa (2) Motion sickness: diphenhydramine (苯海拉明), dimenhydrinate (茶苯海明), promethazine (异丙嗪), meclozine (美克洛嗪) (3) Sedation and insomnia: using drugs with CNS depression

B. Histamine receptor antagonists 3. Adverse effects (1) CNS depression (2) GI reactions (3) Others: arrhythmias, etc.

B. Histamine receptor antagonists Second Generation agents Alkylamines ( 烷基胺) Acrivastine(阿伐斯汀) Piperazines (哌嗪类) Cetirizine (西替利嗪) Phthalazinones Azelastine(氮卓斯汀) Piperidines Levocabastine(左卡巴斯汀) Loratadine(氯雷他定) Fxofenadine(非索非那定)

B. Histamine receptor antagonists Second Generation agents 地氯雷他定氯雷他定非索非那定特非那定阿伐斯汀西替利嗪 Clin Pharmacol Drug Dev. 2016 Jan;5(1):5-12. doi: 10.1002/cpdd.236. Review

B. Histamine receptor antagonists H2 receptor antagonists 1. Pharmacological effects (1) Inhibiting gastric acid secretion (2) Cardiovascular effects: heart stimulating (weaker in therapeutic doses) (3) Immunosuppressive effects 2. Clinical uses (1) Peptic ulcers (2) Adjuvant therapy for cancers 3. Adverse effects GI, CNS, antiandrogen, etc.

H4 R antagonist JNJ 39758979 UR-63325 PF-3893787 toreforant (JNJ 38518168)

H4 receptor: fromorphantotheclinic. Front. Pharmacol.6:65.

Effects of H4R-deficient mice in selected animal models H4 receptor: fromorphantotheclinic. Front. Pharmacol.6:65.