Pharmacology of GABA
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Benzodiazepines, barbiturates, zolpidem, flumazenil, others.
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Pharmacology of GABA
- 1. GABA
- 5. A. Action of benzodiazepines plus anticonvulsant effect, sedation, muscle relaxation GABA-gated Cl--channel Benzodiazepines Unopposed excitation Normal GABA-ergic inhibition Enhanced GABA-ergic inhibition GABA-ergicneuron
- 16. C. Concentration dependence of barbiturate and benzodiazepine effects B. Effect of hypnotics on proportion of REM/NREM Paralyzing Anesthetizing Hypnogenic Hypnagogic Calming, anxiolytic Triazolam Pentobarbital Effect Concentration in blood Pentobarbital Triazolam Barbiturates: Benzo- diazepines:
- 17. Anxiolysis plus anticonvulsant effect, sedation, muscle relaxation Diazepam R1 = Cl R2 = CH3 R3 = R4 = H Benzo diaz epine R4 N N R1 R3 O R2 Inhibition of excitation Hyper- polari- zation GABA GABA-gated Cl--channel Cl- Benzodiazepines Benzodiazepine receptor GABA-receptor Chloride ionophore GABA= γ-amino- butryc acid
- 21. Hypnotics 223 A. Succession of different sleep phases during night rest REM Waking state Sleep stage I Sleep stage IV Sleep stage III Sleep stage II REM-sleep= Rapid Eye Movement sleep NREM = No Rapid Eye Movement sleep Ratio
- 22. B. Effect of hypnotics on proportion of REM/NREM A. Succession of different sleep phases during night rest IV REM-sleep= Rapid Eye Movement sleep NREM = No Rapid Eye Movement sleep Ratio NREM 5 10 15 20 25 30 Nights without hypnotic Nights with hypnotic Nights after withdrawal of hypnotic EffectBarbiturates: REM
- 23. Hypnotics 225 Waking state NREM-sleep Neurons with transmitters: Histamine Acetylcholine Glutamate Norepinephrine GABA A. Transmitters: waking state and sleep
- 24. B. Wake-sleep pattern, stress, and hypnotic drug action A. Transmitters: waking state and sleep Hypnotic 1 2 3 Emotional stress
- 25. B. Wake-sleep pattern, stress, and hypnotic drug action C. Changes of the arousal reaction in the elderly Hypnotic Hypnotic 3 1 2
- 26. Midazolam Diazepam as glucuronide Active metabolites Inactive Oxazepam Nordazepam
- 27. Triazolam Brotizolam Oxazepam Lormetazepam Bromazepam Flunitrazepam Lorazepam Camazepam Nitrazepam Clonazepam Diazepam Temazepam Prazepam Applied drug Active metabolitePlasma elimination half-life Hypnagogic effect Abuse liability Anxiolytic effect 0 20 30 40 50 6010 >60 h