1. α, β-R agonists α-R agonists, β-R agonists
Chapter 8 Adrenoceptor agonists (adrenomimetic drugs, Sympathomimetic amines)
α, β-R agonists
α-R agonists,
β-R agonists

2. Section 1 Structure-activity relationship and classification

3. Chemistry

4. structure-activity relationship
(1) Catecholamine (CA,儿茶酚胺)
(2) -C： block MAO
(3) N- ： or  selective

6. classifications α, β-R agonists: AD,ephedrine（麻黄碱） α-R agonists
α1、α2-R agonists ：NA
α1-R agonists: phenylephrine(去氧肾上腺素)
α2-R agonists：oxymetazoline(羟甲唑啉）apraclonidine(阿可乐定)
β-R agonists,
β1、 β 2-R agonists : Isoprenaline
β1-R agonists ：dobutamine(多巴酚丁胺)
β2-R agonists: salbutamol（沙丁胺醇）

7. section 2 α、 β -R agonists
Adrenaline (AD,肾上腺素)
Ephedrine（麻黄碱）
Dopamine (DA，多巴胺)

8. Adrenaline (epinephrine,AD,肾上腺素)
Source and Chemistry
1. adrenal medulla: pheochromocyte( 嗜铬细胞)
2. PNMT(苯乙胺-N-甲基转移酶)
TH DDC DβH PNMT
Tyr→→→dopa→→→→DA→→→→NA→→→→→AD

9. AD

10. Pharmacokinetics 1. Absorption 2. Termination Uptake
metabolism: MAO/COMT

12. 3.Excretion:VMA (3甲氧4羟扁桃酸)
Normal: 2-6.8mg/24h
Pheochromocytoma:10-250mg /24h
（嗜铬细胞瘤）

13. pharmacological actions: activate α, β-R
1.heart: strongly excited (β1-R)
positive inotropic effect
positive chronotropic effect
positive dromotropic effect
Coronary: dilation
(1)Agonist β2-R
(2)Prolong diastolic phase
(3)Increase myocardial oxygen consumption adenosine↑

14. Advantage and disadvantage

15. 2.vessels: (1) contraction(α-R ) Skin, mucosa: strong Kidney: strong
juxtaglomerular cells(β1-R): Renin release↑
Cerebral :
(2) dilation:
Skeletal Muscle (β2-R)
Coronary:
direct effect: β2-R
indirect effect: time of perfusion ↑
adenosine↑

16. pharmacological actions
3.BP: small dose: SBP↑, DBP ↓
large dose: SBP↑, DBP↑
Double phased response

18. pharmacological actions
4. smooth muscle:
bronchial smooth muscle: 2, 1
Gastrointestinal tract: (negative feedback)
Uterus, bladder: 2
Pupillary dilator muscle: 1

19. pharmacological actions
5. metabolism: ↑ 20%-30%
(1)Carbohydrate: blood Glu ↑
, 2: glycogenolysis↑(糖原分解）
glyconeogenesis↑(糖原异生)
2: insulin↓
: glucagon↑
(2) Lipolysis : blood fatty acid ↑
3 : triglyceride lipase(三酰甘油酶) ↑

20. 6. skeletal muscle
7. CNS

21. clinical uses 1.cardiac arrest 2.allergic shock: first choice cautions
3.bronchial asthma
4.prolongation of local anesthetic duration
5.topical hemorrhage: 0.1%
6. glaucoma

22. adverse reactions Arhythmia Hypertension CNS reactions
contraindications

23. Ephedrine(麻黄碱) 陈克恢（１８９８—１９８８）
药理学家。长期致力于中药药理研究，是２０世纪国际药理学的一代宗师，也是现代中药药理学研究的创始人。他的突出贡献是，首先发现麻黄素的药理作用，为推动交感胺类化合物的化学合成奠定了基础，并为从天然产物中寻找开发新药起了典范作用。他还发现解救急性氰化合物中毒的方法，并被沿用至今。

24. Ephedrine Mechanisms: 1. direct actions：1 ,  1,2 ,  2-R
2. indirect actions
Characteristics:
1. stable, orally.
2. action: slower,weaker and longer VS AD
3. central excitation
4. tachyphylaxis

25. Actions:
1. CNS effects
2. CVS
3. Smooth muscle
4. Increase skeletal muscle tension

26. ephedrine clinical uses 1.bronchial asthma 2.nasal congestion
3.hypotensive states
4. Allergy (urticaria, angioneuroedema)

27. adverse reactions
Cardiac and
CNS excitation

28. dopamine (DA,多巴胺) Pharmacokinetics: ivd, short t1/2, not across BBB
pharmacological actions
activateα, β1 , DA -R, ↑NA release

29. pharmacological actions
1.Cardiovascular system:
vessel: dilation (D1A-R), contraction (α-R)
Small dose: DBP↓ (D1A-R) SBP→
Midddle dose: SBP↑ (β1 -R) DBP↑→
Large dose: DBP↑ (α-R) SBP↑
2. renal vessels : small dose dilation (D1A-R)
large dose contraction (α-R)

30. clinical uses 1.shock 2.chronic heart failure(CHF)
3.acute renal failure (ARF)

31. Mephentermine (美芬丁胺,wyamine,恢压敏)
Similar to ephedrine (direct, indirect)
central excitation
Used to prevent hypotension state
Used to treat nasal congestion

32. section 3 α-R agonists α-R agonists α1、α2-R agonists α1-R agonists

33. 1, 2 Agonists noradrenaline(去甲肾上腺素，norepinephrine，NA，NE)
[source and chemistry]

34. NA

35. pharmacokinetics

37. pharmacological actions
strongly activate α1, α2 -R
slightly activate β1-R.

38. pharmacological actions
1.vessels: contraction(α-R)
coronary vessels :dilation (similar to AD)
presynaptic adrenergic terminals (α2-R):NE ↓
negative feedback
2.heart: excitation(β1-R)
3.BP: small dose: SBP↑ DBP→
large dose: SBP↑ DBP↑
4.others: weaker than AD

40. clinical uses 1.shock：early
2.hypotension caused by drugs’ intoxication
3.upper digestive tract hemorrhage

41. adverse reactions
1.local ischemia and necrosis
2.acute renal failure

42. metaraminol (间羟胺, aramine, 阿拉明)
[Mechanisms]1.direct actions 2.indirect actions
[Characteristics]
1. weaker and longer than NA
2.little adverse reactions: renal failure, arrhythmias
3.tachyphylaxis
[Uses] substitute for NA in treatment of shock

43. 1-R Agonists
Phenylephrine(去氧肾上腺素)
Methoxamine(甲氧明)

44. Phenylephrine and methoxamine
1.selective α1-R agonists: shock, hypotension
2. renal vasoconstriction: significant
3. paroxysmal supraventricular tachycardia
4.phenylephrine→mydriasis(rapid, weak, short)

45. 2-R Agonists Peripheral 2-R Agonists: apraclonidine(阿可乐定): Glaucoma
oxymetazoline(羟甲唑啉)： nasal congestion
apraclonidine(阿可乐定): Glaucoma
Central 2-R Agonists：HBP
clonidine(可乐定)，
methyldopa （甲基多巴）

46. β1、 β2-R agonist β1-R agonists β2-R agonists
Section4 β-R agonists
β1、 β2-R agonist
β1-R agonists
β2-R agonists

47. β1、 β2-R agonist Isoprenaline (Isop,异丙肾上腺素) pharmacological actions:
strongly activate β1、 β2-R

48. pharmacological actions
1.heart: excitation (β1-R)
positive inotropic effect
positive chronotropic effect
positive dromotropic effect

49. pharmacological actions
2.vessels:
Skeletal Muscle blood vessel (β2-R)
Coronary:
direct effect: β2-R
indirect effect:
3.BP: SBP↑ DBP↓

51. pharmacological actions
4. smooth muscle: relaxation
especially bronchial smooth muscle

52. clinical uses 1. cardiac arrest 2. atrial ventricular block(AVB)
3. bronchial asthma

53. β1-R agonists: dobutamine (多巴酚丁胺)
[Characteristics]
1. selective β1-R agonist
2. inotropic effect>chronotropic effect
（ in therapeutic dose）
3. Used in CHF caused by AMI
4. tachyphylaxis

54. β2-R agonists Salbutamal(沙丁胺醇，舒喘灵) Terbutaline(特布他林，间羟舒喘灵)
Clinical use: bronchial asthma