CHEN Zhong CHEN Zhong 陈 陈 陈 陈 Department of Pharmacology, Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang College of Pharmaceutical Sciences, Zhejiang University University [email protected][email protected]陈陈陈陈陈陈 陈陈陈陈陈陈 B402-420 B402-420 , , 88208228 88208228 Sedative-Hypnotic Drugs Sedative-Hypnotic Drugs 2013.6
Sedative-Hypnotic Drugs. CHEN Zhong 陈 忠 Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University [email protected] 医学院科研楼 B402-420 , 88208228. 2013.6. Sedatives (镇静药): 能缓和激动,消除躁动,恢复安静情绪的药物. Hypnotics (催眠药): 能促进和维持近似生理睡眠的药物. - PowerPoint PPT Presentation
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CHEN Zhong CHEN Zhong 陈 忠陈 忠
Department of Pharmacology, Department of Pharmacology,
College of Pharmaceutical Sciences, Zhejiang UniversityCollege of Pharmaceutical Sciences, Zhejiang University
- is characterized by excessive, exaggerated anxiety and worry about everyday life events with no obvious reasons for worry;- can be extremely debilitating, having a serious impact on daily life.
Anxiety
Insomnia:
-1-5%, more in old women; - trouble in falling asleep or too easily to be waken up; - can be primary or secondary; - harmful to daily life: excessive daytime sleepiness and a lack of energy, feel anxious, depressed, or irritable.
Several kinds of sleep deficits
无法入睡浅睡、易醒早醒睡后焦虑、烦躁梦游
嗜睡神经性睡眠障碍
What’s the mechanism?Receptor?Neurotransmitter?Neuropeptide?stimulator pathway?
When should start drug treatment?
Why ethanol produce dual effect?
Molecular Neuropharmacology
Stage 3 & 4, 统称为慢波睡眠
A schematic drawing showing key components of the ascending reticular activating system (ARAS)
(1) Sites of action:(1) Sites of action: mainly acts on mainly acts on limbic systemlimbic system and and midbrain reticular formationmidbrain reticular formation..
(2) Interaction with GABA(2) Interaction with GABAAA receptor receptor
Benzodiazepines bind to specific, high affinity sites on the cell Benzodiazepines bind to specific, high affinity sites on the cell membrane, which are separate from but adjacent to the membrane, which are separate from but adjacent to the receptor for receptor for -aminobutyric acid (GABA).-aminobutyric acid (GABA).
The binding of benzodiazepinesThe binding of benzodiazepines enhances the affinity of GABA receptor for enhances the affinity of GABA receptor for this neurotransmitterthis neurotransmitter, resulting in a more frequent opening of adjacent , resulting in a more frequent opening of adjacent chloride channels.chloride channels. - - coagonistcoagonist
This in turn results inThis in turn results in enhanced hyperpolarizationenhanced hyperpolarization ((超极化超极化)) and further and further inhibition of neuronal firing.inhibition of neuronal firing.
A.A. Benzodiazepines Benzodiazepines
Modulation mode of the central inhibitory transmitter GABA Modulation mode of the central inhibitory transmitter GABA and the action sites of drugsand the action sites of drugs
Action of the central inhibitory transmitter GABA on ClAction of the central inhibitory transmitter GABA on Cl-- influx and the action sites of benzodiazepines (BDZs)influx and the action sites of benzodiazepines (BDZs)
A.A. Benzodiazepines Benzodiazepines
Diazepam Diazepam 地西泮地西泮(安定)(安定)
N
NCl
CH3
O
R1
R2
R3
R4R7
1. 1. Pharmacological effects and clinical usesPharmacological effects and clinical uses
(1) Antianxiety(1) Antianxiety
at small dosesat small doses
acting on limbic systemacting on limbic system ((边缘系统边缘系统,,杏仁核、海杏仁核、海马马))
(2) Sedative-hypnotic effects(2) Sedative-hypnotic effects ((作用于作用于脑干)脑干) at relatively larger doses, no anesthetic effect; at relatively larger doses, no anesthetic effect;
not remarkably affect on REMnot remarkably affect on REM
used forused for insomniainsomnia (失眠)(失眠) andand preanesthetic preanesthetic medicationmedication
A.A. Benzodiazepines Benzodiazepines
NREM
Stages 3
Stages 3 and 4 are deep sleep.Growth hormone is released during these stages.
Slow wave sleep
BZs
(3) Antiepileptic and anticonvulsant effects(3) Antiepileptic and anticonvulsant effects
Convulsion due various causes; Convulsion due various causes; status epilepticusstatus epilepticus ((i.v.i.v.))
(4) Centrally acting muscle relaxant effect(4) Centrally acting muscle relaxant effect Relaxing the spasticity of skeletal muscle, probably by Relaxing the spasticity of skeletal muscle, probably by
increasing presynaptic inhibition in the spinal cord.increasing presynaptic inhibition in the spinal cord.
Used for the treatment of skeletal muscle spasms caused by Used for the treatment of skeletal muscle spasms caused by central or peripheral diseases.central or peripheral diseases.
(5) Others(5) Others Amnesia (Amnesia ( 短暂性记忆缺失短暂性记忆缺失 , i.v., i.v. )) Respiratory and CVS effectsRespiratory and CVS effects
A.A. Benzodiazepines Benzodiazepines
3. 3. Adverse effectsAdverse effects
(1) Central depression(1) Central depression Most common: drowsiness and confusion (Most common: drowsiness and confusion (potentiated by potentiated by
ethanol or other central depressantsethanol or other central depressants). ).
2. 2. Clinical usesClinical usesCentral depressionCentral depressionAdjuvant of migraineAdjuvant of migraine ( ( 偏头痛偏头痛 )) and antipyretic- and antipyretic-
used for central depression caused by drugs or used for central depression caused by drugs or diseases; mild depression;diseases; mild depression; child hyperactivitychild hyperactivity; ; enuresis; enuresis; etc.etc.
Meclofenoxate Meclofenoxate 甲氯芬酯(氯酯醒)甲氯芬酯(氯酯醒)
Adjuvant of central depressive diseases; Adjuvant of central depressive diseases; enuresis; enuresis; etc.etc.
A A Psychomotor stimulants Psychomotor stimulants
Nikethamide Nikethamide 尼可刹米尼可刹米
N
C
C2H5
C2H5
N
O
B B Respiratory center stimulants Respiratory center stimulants
B B Respiratory center stimulants Respiratory center stimulants
1. 1. Pharmacological effectsPharmacological effects DirectDirect (respiratory centre)(respiratory centre) and indirectand indirect (reflex via (reflex via