1. Chapter 6
항우울약물
Antidepressants

2. Depression and Mania Decreasing of Biogenic monoamine Biogenic amines
NE or Serotonin
Increasing of Biogenic monoamine

3. Episode of MAOI as antidepressant

4. Biogenic amine and Function
Serotonin and NE affect depressive mood
Serotonin NE

5. Biosynthesis of serotonin(5-HT) and NE

6. Criteria for Depression
5 symptoms of left items
depressed mood or loss of interest

8. Disease and Drugs associated with Depression

9. Antidepressants Tricyclic antidepressant MAO Inhibitor
Serotonin Uptake Inhibitor

10. The site of action of Antidepressant at NE

11. The site of action of antidepressant at Serotonin

12. Structures of Antidepressants
Structure of Antidepressant
- Dihydordibenzazepines(imipramine, clomipramine)
- Dihydrodibenzocycloheptenes(amitriptyline, nortriptyline)
- Dibenzoxepins & Dibenzothiepins(doxepin, dothiepin)
- Arylpiperazines
- Non Tricyclics (mianserin, mirtazapine, bupropion, fluoxetine, trazodone)

13. Therapeutic Application
The mechanism of TCA
Therapeutic Application
-Severe depression
Phobiasis
Enuresis: Control the bed-wetting by contraction of internal sphincter of the bradder

14. Drug interaction of TCA

15. The mechanism of MAOI

16. Metabolism of Biogenic amine
MAOI
Increase the Conc. of biogenic amine

17. Monoamine Oxidase
MAOI

18. The Mechanism of MAOI

19. MAO-A,-B and Cheese Effect
MAO-A preferentially deaminate Serotonin, Epinephrine and Norephinephrine
MAO-A Inhibitor: Antidepressant
MAO-A
MAO-B
MAO-B:
MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types.
MAO-B Inhibitor: Antiparkinson activity
Cheese Effect
Cheese Effect:
MAOIs inhibit the catabolism of dietary amines. When foods containing tyramine are consumed (so-called "cheese effect"), the individual may suffer from hypertensive crisis. If foods containing tryptophan are consumed, hyperserotonemia may result

20. Tyramine

21. Cheese Effect Of MAOI Sublingual Nipedipine or Captopril(ACEI)
Hypertensive Crisis
Release of NE
Tyramine
Sublingual Nipedipine or Captopril(ACEI)
Food : Cheese, wine, beer, yeast product

22. Dietary & Medication Restriction for MAOI
Food
Drugs
Cheese, Yogrut
Asthma inhalant
Beer, Wine
amphetamine
Fermented food
Appetite supressant
Soy Sauce, Bean
Ephedrine
Coffee
Sumatrytan
Etc.
Containing Tyramine
Monoamine drugs

23. The receptor specificty of SSRI
Low adverse effect

24. The clinical application of SSRI
Advantage
Low side effect
Most widely used in US
Therapeutic use
Bulima nervosa(신경성과식)
Obssesive compulsive disorder(강박신경증)
Side effect
Nausea(구역)
Anxiety
Insomnia(불면)
Sexual dysfunction
Anorexia(식욕부진)
Weigh loss

25. Therapeutic application of Antidepressants

26. Imipramine
5-(3-Dimethylaminopropyl)-10,11-dihydro-5H-dibenzo[b,f]azepine hydrochloride
10,11-Dihydro-N,N-dimethyl-5H-dibenzo[b,f]azepine-5-propanamine hydrochloride
Tofranil® (Norvatis), 이미프라민정 (환인, 영풍), Antideprin® (Ciba-Geigy)
Dihydrodibenzazepine계

27. Tricycles(6,6,6)

28. Tricycles(6,7,6)

29. Imipramine
Retrosynthesis

30. Imipramine
Synthesis A
Synthesis of A

31. Clomipramine
3-chloro-5-(3-dimethylaminopropyl)-10,11-dihydro-5H-dibenzo[b,f]azepine hydrochloride
Anafranil® (Tyco Hilthecare/Norvatis), 염산 클로미프라민 캅셀 (환인)
Dihydrodibenzazepine계

32. Clomipramine
Retrosynthesis

33. Clomipramine
Synthesis

34. Amitriptyline
5‑(3-dimethylaminopropylidene)dibenzo[a,d][1,4]cycloheptadiene hydrochloride
5‑(γ-dimethylaminopropylidene)-5H-dibenzo[a,d]-10,11-dihydrocycloheptene hydrochloride
Elavil® (Merck), 에나폰 정 (환인), 에트라빌 정 (동화), 염산아미프리프틸 정 (명인)
Dihydrodibenzocycloheptene계

35. Amitriptyline
Retrosynthesis I
SN Rx
Grignard Rx
& Dehydration

36. Amitriptyline
Synthesis I A
Synthesis of A

37. Amitriptyline
Retrosynthesis II

38. Amitriptyline
Synthesis II

39. Clinical application to Nocturnal enuresis(bed wetting)

40. Nortriptyline Not Dimethyl Monomethyl
3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine
hydrochloride
5-(γ-Methylaminopropylidene)dibenzo[a,d]cyclohepta-1,4-diene hydrochloride
Aventyl® (Lanbaxy), 센시발 정 (일성)
Dihydrodibenzocycloheptene계

41. Nortriptyline
Retrosynthesis

42. Nortriptyline
Synthesis

43. Doxepin
(E,Z)-3-(Dibenzo[b,e]oxepin-11(6H)-ylidene)-N,N-dimethylpropan-1-amine
Sinequan® (Pfizer), 루시펜 크림 (삼천당), 세피드린 크림 (이알엔)
Dibenzoxepin 계

44. Retrosynthesis
Doxepin

45. Synthesis
Doxepin

46. Dothiepin
(E,Z)-3-(Dibenzo[b,e]thiepin-11H(6H)-ylidene)-N,N-dimethylpropan-1-amine
푸로치아덴 캡슐 (삼일)
Dibenzothiepin계

47. Retrosynthesis
Dothiepin

48. Synthesis
Dothiepin

49. Mianserin
1,2,3,4,10,14b-Hexahydro-2-methyldibenzo[c,f]pyrazino[1,2-a]azepine
볼비돈 정(오가논)
비삼환계

50. Retrosynthesis
Mianserin

51. Synthesis
Mianserin

52. Mirtazapine
1,2,3,4,10,14b-Hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c][2]benzazepine
Remeron® (Organon), 레믹실 오디티 정 (명인), 미르락스 정/오디티 정 (산도즈),
레메론 정/솔탭 정 (쉐링-푸라우)
비삼환계

53. Retrosynthesis
Mirtazapine

54. Synthesis
Mirtazapine

55. Bupropion
(+,+)-1-(3-Chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride
Wellbutrin® (GSK), 웰부트린 서방정 (글락소스미스클라인)
비삼환계

56. Bupropion
Retrosynthesis

57. Bupropion
Synthesis

58. Fluoxetine
(+)-N-Methyl-3-[4-(trifluoromethyl)phenoxy]benzenepropan-1-amine
Prozac® (Lilly), 프로작 캡슐 (릴리), 폭세틴 캡슐 (환인, 신풍), 푸로핀 캡슐 (드림파마),
푸록틴 캡슐 (명인)
비삼환계

60. Drug Interaction and side effects of prozac

61. Fluoxetine
Retrosynthesis

62. Synthesis
Fluoxetine

63. Trazodone HCl
2-[3-[4-(3-Chlorophenyl)piperazin-1-yl]propyl]-[1,2,4]triazolo[4.5-a]pyridin-3-one
2-(3-[4-(3-Chlorophenyl)piperazin-1-yl]propyl)-[1.2.4]triazolo[4,3-a]pyridin-3(2H)-one
티리티코 정/ 국제, 트라조돈 캄셀(명인)
비삼환계

64. Retrosynthesis
Trazodone HCl

65. Synthesis
Trazodone HCl