Sedative-hypnotics, Antiepileptics and Psychotherapeutic Drugs

Sedative-hypnotics Antiepileptics Psychotherapeutic Drugs

Sedative-hypnotics Benzodiazepines Barbiturates

1. Benzodiazepines

1). 1960

1). ChlordiazepoxideLibrium60

1). DiazepamValium

R1R2R3R4XNamesCH3HHClOHHHNO2OHHClNO2O(CH2)2N(C2H5)2HFClOCH3HFClO CH2 HFClOHOHHClOCH3OHHClOHOHClClOCH2CF3HFClS

1). 1, 2

R1R2NamesHHEstazolamCH3HAlprazolamCH3ClTriazolam

1). 1, 2Midazolam Loprazolam

1). 4, 5

R1R2R3R4NamesCH3HClHOxazolamHFBrHHaloxazolamHClClHCloxazolamCH3ClClHMexazolamHFClCH2CH2OHFlutazolam

1).

RNamesC2H5EtizolamBrBrotizolam

2). A7NO2CF3BrCl689

2). B1 1N 2

2). B2 3 4, 5 5 1, 24, 5

2). C 2 ClFBrNO2CF3H 2 34

2). 3B

3). GABAGABACl-Cl- Cl-GABAGABACl-

Flumazenil

4).

5).

6).

Diazepam

45

13

Chemical name of Diazepam 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one 3H- or 1H-1,4-Benzodiazepine1,2-Dihydro-3H-2,3-Dihydro-1H- 1,4-benzodiazepine1,3-Dihydro-2H-

6).

Diazepam

BZR1 Zolpidem

Sedative-hypnotics Benzodiazepines Barbiturates

2. Barbiturates

1). Barbituric acid Barbiturates

2). 1

R1 R2 R3 X Barbital C2H5 C2H5 H O 4-12h Phenobarbital C2H5 C6H5 H O 4-12h

2). 2

R1 R2 R3 X Amobarbital C2H5 CH2CH2CH(CH3)2 H O 2-8h Cyclobarbital C2H5 H O 2-8h

2). 3

R1 R2 R3 X Secobarbital CH2CH=CH2 H O 1-4h Pentobarbital C2H5 H O 2-4h

2). 4

R1 R2 R3 X Hexobarbital CH3 CH3 O 1h Thiopental sodium C2H5 H -S-Na 0.75h

3).

Lactam LactimBarbituric acid Monolactim Dilactim Trilactim

1-5-1,3-1,5-5,5-

pHpH+ CO2

4).

1lgP2.054 ~ 107 ~ 8OHNH2RNHCOCOOHSO3H

2NN2CNS2,4-2,4,6-

5). 151

4). 252

4). 353

4). 4

4). 5

4). 6N

Sedative-hypnotics Benzodiazepines Barbiturates

3. 1

3. 2 Delta sleep inducing peptide, DSIP Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu Melatonin

Sedative-hypnotics Antiepileptics Psychotherapeutic Drugs

Antiepileptics

11 Phenobarbital 1912 Mephobarbital 1935 Metharbital 1952

12 Phenobarbital Primidone 1954

21 Hydantoins Phenytoin (sodium) 1938

Mephenytoin Ethotoin 1947 1957

22 Oxazolidinediones

Trimethadione Paramethadione 1946 1949

23 Succinimides

Phensuximide Methsuximide 1953 1957 Ethosuximide 1960

24

Phenacemide 1951

X BarituratesPhenobarbitalHydantoins Phenytoin sodium OxazolidinedionesTrimethadione SuccinimidesEthosuximidePhenacemide

3 Diazepam Clobazam Nitrozepam Clonazepam Lorazepam Midazolam

4 Carbamazepine Oxcarbazepine1974

5 Sodium valproate Valpromide1978GABA

61GABA

62GABA Halogabide Gabapentin

Halogabide

63GABA Vigabatrin

71GABA

72

Sedative-hypnotics Antiepileptics Psychotherapeutic Drugs

2019381928ACh19481970FDA19521950

19581968Carlson5-2000Nobel1987941954FDA195419601963

Psychotherapeutic Drugs Antipsychotic drugs Antischizophrenic drugs Antianxiety drugs Antidepressant drugs Antimanic drugs

Antipsychotic drugs-1 Antischizophrenic drugs Phenothiazines Thioxanthenes Butyrophenones Diphenylbutylpiperidines

Antipsychotic drugs-2 Antischizophrenic drugs Benzamides Dibenzodiazepines and Dibenzoxazepines Hydroindolones

1 Phenothiazines 1)2)3)4)5)

1) Promethazine

R1R2 ChlorpromazineN(CH3)2Cl1 AcetylpromazineN(CH3)2COCH3

R1R2 TrifluoperazineCF313 Thiethylperazine SC2H5 ThioridazineSCH3-1 PipotiazineSO2N(CH3)2 MesoridazineSOCH3

2)1 21, 3, 42 CF3 > Cl > COCH3 > H > OH2

2)2 3,

2)3 -O-, -CH2-, -CH=CH-, -CH2CH2--C=

ABC B > C > A BR,>

CN-S22 A

3)

5)

2 Thioxanthenes1

RX ChlorprothixeneN(CH3)2Cl ThiothixeneSO2N(CH3)2 FlupenthixolCF3 ZuclopenthixolCl

2 Thioxanthenes22Zcis-isomerEtrans-isomer cis > trans

3 Butyrophenones 1

R1R2 HaloperidolOH BromoperidolOH TrifluperidolOH

3 Butyrophenones 2

R1R2 BenperidolH TimiperoneH PipamperoneCONH2

3 Butyrophenones 3

3 Butyrophenones 4

4 Diphenylbutylpiperidines1

4 Diphenylbutylpiperidines2

5 Benzamides 1D2

5 Benzamides 2D2

6 Dibenzodiazepines and Dibenzoxazepines

XR1R2R3 ClozapineNHHClCH3 ClothiapineSClHCH3 LoxapineOClHCH3 AmoxapineOClHH

7 Hydroindolones

81

82

Psychotherapeutic Drugs Antipsychotic drugs Antischizophrenic drugs Antianxiety drugs Antidepressant drugs Antimanic drugs

Antidepressant drugs Norepinephrine-reuptake inhibitors5 Serotonin-reuptake inhibitors Monoamine oxidase inhibitors Atypical antidepressants

11

R1R2 ImipramineH(CH2)3N(CH3)2 DesipramineH(CH2)3NHCH3 ClomipramineCl(CH2)3N(CH3)2 TrimipramineHCH2CH(CH3)CH2N(CH3)2

12

13

25Serotonin-reuptake inhibitors1

25Serotonin-reuptake inhibitors2

3 Monoamine oxidase inhibitors1

3 Monoamine oxidase inhibitors2MAOA

4Atypical antidepressants1

4Atypical antidepressants2

1

2