GABA

Psychopharmacologicals 227

A. Action of benzodiazepines

Anxiolysis

plus anticonvulsant effect,sedation, muscle relaxation

Diazepam

R1 = Cl

R2 = CH3R3 = R4 = H

Benzo

diaz

epine

R4

N

N

R1

R3

OR2

Inhibition ofexcitation

Hyper-polari-zation

GABA

GABA-gated Cl--channel

Cl-

Benzodiazepines

Unopposed excitationNormalGABA-ergic inhibition

EnhancedGABA-ergic inhibition

GA

BA

-erg

ic n

euro

n

Benzodiazepinereceptor

GABA-receptor

Chlorideionophore

GABA=γ-amino-butryc acid

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Hypnotics 223

C. Concentration dependence of barbiturate and benzodiazepine effects

B. Effect of hypnotics on proportion of REM/NREM

A. Succession of different sleep phases during night rest

REM

Wakingstate

SleepstageI

SleepstageIV

SleepstageIII

SleepstageII

REM-sleep= Rapid Eye Movement sleep NREM = No Rapid Eye Movement sleep

Ratio

NREM

5 10 15 20 25 30Nightswithouthypnotic

Nightswithhypnotic

Nights afterwithdrawalof hypnotic

Paralyzing

Anesthetizing

Hypnogenic

Hypnagogic

Calming, anxiolytic

Triazolam

Pentobarbital

Effect

Concentration in blood

Pentobarbital

Triazolam

Barbiturates:

Benzo-diazepines:

REM

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Psychopharmacologicals 227

A. Action of benzodiazepines

Anxiolysis

plus anticonvulsant effect,sedation, muscle relaxation

Diazepam

R1 = Cl

R2 = CH3R3 = R4 = H

Benzo

diaz

epine

R4

N

N

R1

R3

OR2

Inhibition ofexcitation

Hyper-polari-zation

GABA

GABA-gated Cl--channel

Cl-

Benzodiazepines

Unopposed excitationNormalGABA-ergic inhibition

EnhancedGABA-ergic inhibition

GA

BA

-erg

ic n

euro

n

Benzodiazepinereceptor

GABA-receptor

Chlorideionophore

GABA=γ-amino-butryc acid

Lüllmann, Color Atlas of Pharmacology © 2000 ThiemeAll rights reserved. Usage subject to terms and conditions of license.

Hypnotics 223

C. Concentration dependence of barbiturate and benzodiazepine effects

B. Effect of hypnotics on proportion of REM/NREM

A. Succession of different sleep phases during night rest

REM

Wakingstate

SleepstageI

SleepstageIV

SleepstageIII

SleepstageII

REM-sleep= Rapid Eye Movement sleep NREM = No Rapid Eye Movement sleep

Ratio

NREM

5 10 15 20 25 30Nightswithouthypnotic

Nightswithhypnotic

Nights afterwithdrawalof hypnotic

Paralyzing

Anesthetizing

Hypnogenic

Hypnagogic

Calming, anxiolytic

Triazolam

Pentobarbital

Effect

Concentration in blood

Pentobarbital

Triazolam

Barbiturates:

Benzo-diazepines:

REM

Lüllmann, Color Atlas of Pharmacology © 2000 ThiemeAll rights reserved. Usage subject to terms and conditions of license.

Hypnotics 223

C. Concentration dependence of barbiturate and benzodiazepine effects

B. Effect of hypnotics on proportion of REM/NREM

A. Succession of different sleep phases during night rest

REM

Wakingstate

SleepstageI

SleepstageIV

SleepstageIII

SleepstageII

REM-sleep= Rapid Eye Movement sleep NREM = No Rapid Eye Movement sleep

Ratio

NREM

5 10 15 20 25 30Nightswithouthypnotic

Nightswithhypnotic

Nights afterwithdrawalof hypnotic

Paralyzing

Anesthetizing

Hypnogenic

Hypnagogic

Calming, anxiolytic

Triazolam

Pentobarbital

Effect

Concentration in blood

Pentobarbital

Triazolam

Barbiturates:

Benzo-diazepines:

REM

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Hypnotics 225

B. Wake-sleep pattern, stress, and hypnotic drug action

Waking state NREM-sleep

Neurons withtransmitters:

HistamineAcetylcholineGlutamateNorepinephrineGABA

A. Transmitters: waking state and sleep

C. Changes of the arousal reaction in the elderly

Hypnotic

Hypnotic

1

2

3

1

2

Emotional stress

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Hypnotics 225

B. Wake-sleep pattern, stress, and hypnotic drug action

Waking state NREM-sleep

Neurons withtransmitters:

HistamineAcetylcholineGlutamateNorepinephrineGABA

A. Transmitters: waking state and sleep

C. Changes of the arousal reaction in the elderly

Hypnotic

Hypnotic

1

2

3

1

2

Emotional stress

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Hypnotics 225

B. Wake-sleep pattern, stress, and hypnotic drug action

Waking state NREM-sleep

Neurons withtransmitters:

HistamineAcetylcholineGlutamateNorepinephrineGABA

A. Transmitters: waking state and sleep

C. Changes of the arousal reaction in the elderly

Hypnotic

Hypnotic

1

2

3

1

2

Emotional stress

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Psychopharmacologicals 229

B. Rate of elimination of benzodiazepines

A. Biotransformation of benzodiazepines

Midazolam Diazepam

as glucuronide

Active metabolites

Inactive

Oxazepam

Nordazepam

Triazolam

Brotizolam

Oxazepam

Lormetazepam

Bromazepam

Flunitrazepam

Lorazepam

Camazepam

Nitrazepam

Clonazepam

Diazepam

Temazepam

Prazepam

Applied drug Active metabolitePlasma elimination half-life

Hypnagogiceffect

Abuseliability

Anxiolytic effect

0 20 30 40 50 6010 >60 h

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Psychopharmacologicals 229

B. Rate of elimination of benzodiazepines

A. Biotransformation of benzodiazepines

Midazolam Diazepam

as glucuronide

Active metabolites

Inactive

Oxazepam

Nordazepam

Triazolam

Brotizolam

Oxazepam

Lormetazepam

Bromazepam

Flunitrazepam

Lorazepam

Camazepam

Nitrazepam

Clonazepam

Diazepam

Temazepam

Prazepam

Applied drug Active metabolitePlasma elimination half-life

Hypnagogiceffect

Abuseliability

Anxiolytic effect

0 20 30 40 50 6010 >60 h

Lüllmann, Color Atlas of Pharmacology © 2000 ThiemeAll rights reserved. Usage subject to terms and conditions of license.