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