激动剂
Multi tool use激动剂（或稱：刺激劑/促進劑/活化劑）（英语：agonist）是与受体结合並使之激活，产生生理反应的化合物。激动剂按来源分为内源激动剂和外源激动剂，按效能分为完全激动剂、超激动剂、部分激动剂、反激动剂等。
激动剂分类
内源激动剂（如激素和神经递质）和外源激动剂（如药物）都能激活受体。生理激动剂虽不与受体结合，但仍可产生相同生理反应。
内源性激动剂由身体自然产生，结合並激活特定受体，例如血清素作用于血清素受体，多巴胺作用于多巴胺受体[1]。
外源性激动剂中有完全激动剂、超激动剂和部分激动剂。完全激动剂结合並激活受体，产生完全的效能，有100%的内在活性。比如药物异丙肾上腺素，它能模拟肾上腺素作用于肾上腺素受体；还有吗啡，能模拟多巴胺作用于遍布中枢神经系统的μ-阿片受体。超级激动剂产生的反应比内源激动剂更大，也就是说它有大于100%的内在活性。这未必意味着它比内源激动剂更有效，只是说如果它与受体完全结合，则可以产生更强烈的反应。部分激动剂（如丁螺环酮、阿立哌唑、丁丙诺啡和氯氮平）也会结合並激活受体，但即便它完全与受体结合，也只有部分内在活性。因此诸如丁丙诺啡那样的药品可以治疗鸦片成瘾，因为它们作用在鸦片受体上只产生部分效果，从而依赖性低，不易滥用。
反激动剂与激动剂结合在相同的受体上，不过它非但像拮抗剂一样不产生药理效果，而且还抑制了激动剂的效果，如rimonabant是大麻素的反激动剂。
协同激动剂和其他协同激动剂一起作用产生效果，如NMDA受体就需要谷氨酸、甘氨酸和D-丝氨酸共同激活。
不可逆激动剂与受体以共价键永久结合，已有一些不可逆激动剂的描述[2][3]。
选择性激动剂选择性地结合特定种类的受体，如丁螺环酮作用于血清素5-HT1A。新的发现拓展了药理学对激动剂的传统定义——有的配体在同一受体上既可以表现为激动剂，又可以表现为拮抗剂，这取决于效应路径和组织类型。
新的发现拓展了药理学对激动剂的传统定义——有的配体在同一受体上既可以表现为激动剂，又可以表现为拮抗剂，这取决于效应路径和组织类型。这种现象称为“功能选择性”[4][5]和“选择性受体调控”[6]。
活性
效价强度
激动剂的效价强度反比于其EC50值。EC50是指引起最大反应的一半所需的浓度[7]。EC50非常有助于比较具有相似效能和生理效果的药品的效价强度。[8]这个值越低，激动剂的效价强度就越高，产生最大生理反应所需的药物浓度就越低，[9]副作用也越少。[10]
治疗指数
当药物用于治疗时，很有必要了解达到理想效果所需的剂量和产生不良（甚至可能危险）的副作用的剂量之间的余地。前者以ED50量度，后者以TD50（即在50%个体中产生毒性的剂量）量度，但早期也有用LD50（半數致死量）來表示有不良作用的剂量。TD50与ED50的比值称为治疗指数[11]。一般来说，药物疗效指数越低，该药有效和有毒之间的余地越小，就越容易产生不良副作用。因此疗效指数强调有用的药物除了具有疗效之外，重要的是要留有安全余地。
参考文献
^ Goodman and Gilman's Manual of Pharmacology and Therapeutics. (11th edition, 2008). p14. ISBN 0-07-144343-6
^ De Mey JGR, Compeer MG, Meens MJ. Endothelin-1, an Endogenous Irreversible Agonist in Search of an Allosteric Inhibitor. Mol Cell Pharmacol. 2009, 1 (5): 246–257.
^ Rosenbaum DM, Zhang C, Lyons JA, Holl R, Aragao D, Arlow DH, Rasmussen SG, Choi HJ, Devree BT, Sunahara RK, Chae PS, Gellman SH, Dror RO, Shaw DE, Weis WI, Caffrey M, Gmeiner P, Kobilka BK. Structure and function of an irreversible agonist-β(2) adrenoceptor complex. Nature. January 2013, 469 (7329): 236–40. PMC 3074335. PMID 21228876. doi:10.1038/nature09665.
^ Kenakin T. Inverse, protean, and ligand-selective agonism: matters of receptor conformation. FASEB J. March 2001, 15 (3): 598–611. PMID 11259378. doi:10.1096/fj.00-0438rev.
^ Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H; 等. Functional selectivity and classical concepts of quantitative pharmacology. J. Pharmacol. Exp. Ther. January 2007, 320 (1): 1–13. PMID 16803859. doi:10.1124/jpet.106.104463.
^ Smith CL, O'Malley BW. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr. Rev. February 2004, 25 (1): 45–71. PMID 14769827. doi:10.1210/er.2003-0023.
^ EC50的定义
^ Lees P, Cunningham FM, Elliott J; Cunningham; Elliott. Principles of pharmacodynamics and their applications in veterinary pharmacology. J. Vet. Pharmacol. Ther. 2004, 27 (6): 397–414. PMID 15601436. doi:10.1111/j.1365-2885.2004.00620.x.
^ Patrick, Graham L. An Introduction to Medical Chemistry. 2009-03: 62. ISBN 9780199234479.
^ Swinney DC. Biochemical mechanisms of drug action: what does it take for success?. Nature reviews. Drug discovery. 2004, 3 (9): 801–8. PMID 15340390. doi:10.1038/nrd1500.
^ Muller, Patrick Y.; Milton, Mark N. The determination and interpretation of the therapeutic index in drug development. Nature Reviews Drug Discovery. 2012, 11 (10): 751–761. ISSN 1474-1776. PMID 22935759. doi:10.1038/nrd3801.
药理学一览
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| | 药代动力学 | |
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| | 药效学 |
抗微生物药效学：最小抑菌浓度/抑菌剂
最低杀菌浓度/杀细菌剂
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|---|
| | 激动与拮抗 |
激动剂：反激动剂
- 不可逆激动剂
- 部分激动剂
- 超激动剂
- 生理激动剂
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| | 其他 | |
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| | 相关领域/子领域 | |
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神經調節
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| | 種類 | - ♦ 轉運體 [再攝取]: 增強劑 (RE)
抑制劑 (RI)
釋放劑 (RA)
- ♦ 異構調節 : 正向異位調節 (PAM)
負向異位調節 (NAM)
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|---|
| | Classes |
酶 | 詳見Template:酶抑制
|
|---|
| 离子通道 |
钙离子通道阻滞剂 (CCB)
鉀離子通道阻滯劑 (PCB)
鈉離子通道阻滯劑 (SCB)
鉀離子通道開放劑 (PCO)
|
|---|
|
受體 &轉運體
|
生物胺/单胺类神经递质
|
腎上腺素 |
肾上腺素受体激动药 (α
β (1
2))
腎上腺素受體拮抗劑 (α (1
2), β)
去甲腎上腺素再攝取抑製劑 (NRI)
|
|---|
| 多巴胺 | - 多巴胺受體激動劑
- 多巴胺受體拮抗劑
多巴胺再攝取抑制劑 (DRI)
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| 組織胺 | |
|---|
| 血清素 | - 血清素受體激動劑
血清素受體拮抗劑 (5-HT3)
血清素再攝取抑制劑 (SRI)
|
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|
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| 氨基酸 |
GABA | - GABA受體刺激劑
- GABA受體拮抗劑
GABA再攝取抑制劑 (GRI)
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| 谷氨酸 |
Glutamate receptor agonist (AMPA)
Glutamate receptor antagonist (NMDA)
- Glutamate reuptake inhibitor
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|
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| 膽鹼 |
Acetylcholine receptor agonist (Muscarinic
Nicotinic)
抗膽鹼劑 (Muscarinic
Nicotinic (Ganglionic
神经肌肉阻滞药))
|
|---|
| Cannabinoidergic | - 大麻素
- Cannabinoid receptor antagonist
Endocannabinoid enhancer (eCBE)
Endocannabinoid reuptake inhibitor (eCBRI)
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| Opioidergic | - Opioid modulator
- 鴉片類藥物
- Opioid receptor antagonist
- Enkephalinase inhibitor
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| 其他 |
Adenosine reuptake inhibitor (AdoRI)
- 血管紧张素II受体拮抗剂
- Endothelin receptor antagonist
- NK1 receptor antagonist
- Vasopressin receptor antagonist
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| 其他 |
辅因子 (參見Template:酶辅因子)
前体 (參見Template:氨基酸)
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