Classification of CNS drugs Antipsychotic drugs depression － mania Dementia Sedative-hypnotics Epilepsy and convulsion convulsion Parkinson disease Analgesics Central stimulants Neurological （ general and special ） Psychological

Part 7 Sedative-Hypnotic Drugs §Benzodiazepines §Barbiturates §Others

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 中枢抑制药多数随剂量增加而出现镇静、催眠 等中枢抑制作用，故合称为镇静催眠药 （ sedative-hypnotics ）

Circadian rhythms of physiological functions: different functions in the waking and sleeping Enhanced alertness

Phases of the sleeping

A. Benzodiazepines Diazepam 地西泮 （安定）

§1. Pharmacological effects and clinical uses §(1) Antianxiety § at small doses § acting on limbic system §(2) Sedative-hypnotic effects § at relatively larger doses, no anesthetic effect; § not remarkably affect on REM § used for insomnia and preanesthetic medication A. Benzodiazepines

§(3) Antiepileptic and anticonvulsant effects § convulsion due various causes; status epilepticus (i.v.) §(4) Centrally acting muscle relaxant effect § relaxing the spasticity of skeletal muscle, probably by increasing presynaptic inhibition in the spinal cord. § used for the treatment of skeletal muscle spasms caused by central or peripheral diseases. §(5) Others § amnesia ( 短暂性记忆缺失, i.v. ） § respiratory and CVS effects A. Benzodiazepines

§2. Mechanisms of actions §(1) Sites of action: mainly acts on limbic system and midbrain reticular formation. §(2) Interaction with GABA A receptor §Benzodiazepines bind to specific, high affinity sites on the cell membrane, which are separate from but adjacent to the receptor for  -aminobutyric acid (GABA). §The binding of benzodiazepines enhances the affinity of GABA receptor for this neurotransmitter, resulting in a more frequent opening of adjacent chloride channels. - coagonist §This in turn results in enhanced hyperpolarization （超极化） and further inhibition of neuronal firing. A. Benzodiazepines

Modulation mode of the central inhibitory transmitter GABA and the action sites of drugs

Action of the central inhibitory transmitter GABA on Cl - influx and the action sites of benzodiazepines (BDZs) GABA BDZs

The ascending arousal system, from the rostral pons through the thalamus and hypothalamus, modulates arousal and consciousness - Targets of sedative-hypnotics

AChNE DA 5-HT

Centrally acting muscle relaxant effect: increasing presynaptic inhibition in the spinal cord

§3. Adverse effects §(1) Central depression §Most common: drowsiness and confusion (potentiated by ethanol or other central depressants) §Ataxia; cognitive impairment §Antagonized by BZ receptor antagonist flumazenil （氟马西尼） §(2) Tolerance and dependence §Withdrawal syndrome: central excitation A. Benzodiazepines

§(3) Others §local pain, respiratory and CVS reactions (i.v.) §teratogenic effects §(4) Contraindications §Myasthenia gravis §Infants < 6 months §Pregnancy and lactation mothers §Elderly, heart/lung/liver/kidney dysfunction §Fine motor coordination A. Benzodiazepines

§Other benzodiazepines §According to the metabolisms §Long-acting ： §diazepam, chlordiazepoxide ( 氯氮卓 ), flurazepam ( 氟西泮 ) §Intermediate-acting ： §Nitrozepam ( 硝西泮 ), flunitrozepam ( 氯硝西泮 ), §oxazepam ( 奥沙西泮 ), estazolam ( 艾司唑仑 ） §Short-acting ： triazolam ( 三唑仑 ) A. Benzodiazepines 艹

Phenobarbital 苯巴比妥 B. Barbiturates

§1. ADME § Inducing hepatic enzymes § Alkalining urine: excretion  §2. Pharmacological effects and clinical uses §(1) Sedative-hypnotic effects §(2) Preanesthetic medication §(3) Antiepileptic and anticonvulsant effects B. Barbiturates

§3. Adverse effects §(1) Central depression: including after effect §(2) Tolerance and dependence: long-term uses §(3) Acute poisoning § supporting therapies § alkalizing urine § hemodialysis B. Barbiturates

§Chloral hydrate 水合氯醛 §Sedative-hypnotic effects §Anticonvulsant effect: usually used in children §Hydroxyzine 羟嗪（安泰乐） §Meprobamate 甲丙氨酯（眠而通） §Buspirone 丁螺环酮 §Methaqualone 甲喹酮（安眠酮） C. Others

§Antihistamines 抗组胺药 §Ethanol 乙醇 §Melatonin 褪黑素 C. Others

Part 8 Central stimulants §Psychomotor stimulants §Respiratory center stimulants

D. Central stimulants Psychomotor stimulants (mainly acting on cerebral cortex) Xanthines: caffeine 咖啡因 Related drugs Respiratory center stimulants Direct stimulation Indirect stimulation (reflex) A Psychomotor stimulants

Caffeine 咖啡因 A Psychomotor stimulants

§1. Pharmacological effects §(1) Central stimulation §(2) CVS effects: cardiac stimulation, dilatation of vessels §(3) Relaxing smooth muscles: airways, GI §(4) Other effects: Gastric acid secretion, diuretic effect §(5) Mechanisms of action ： inhibiting PDE- cAMP  ； antagonizing A 1 adenosine receptor & GABA receptor A Psychomotor stimulants

§2. Clinical uses §Central depression §Adjuvant of migraine and antipyretic-analgesic drugs §3. Adverse effects §Central excitation §Convulsion (overdose) A Psychomotor stimulants

§Methylphenidate 哌甲酯（利他灵） §used for central depression caused by drugs or diseases; mild depression; child hyperactivity; enuresis; etc. §Meclofenoxate 甲氯芬酯（氯酯醒） §Adjuvant of central depressive diseases; enuresis; etc. A Psychomotor stimulants

Nikethamide 尼可刹米 B Respiratory center stimulants

§1. Pharmacological effects §Direct (respiratory centre) and indirect (reflex via chemoreceptor) stimulation §2. Clinical uses §Respiratory failure §3. Adverse effects §Elevation of BP, tachycardia, tremor, convulsion

§Dimefline 二甲弗林 （回苏灵） §Direct stimulation §Lobeline 洛贝林（山梗菜碱） §Indirect stimulation B Respiratory center stimulants