Classification of CNS drugs

Classification of CNS drugsClassification of CNS drugs

Antipsychotic drugsAntipsychotic drugsdepressiondepression －－ maniamaniaDementiaDementia

Sedative-hypnoticsSedative-hypnoticsEpilepsy and Epilepsy and convulsionconvulsionParkinson diseaseParkinson diseaseAnalgesicsAnalgesicsCentral stimulantsCentral stimulants

NeurologicalNeurological （（ ggeneral and specialeneral and special ））

PsychologicalPsychological

Part 7Part 7

Sedative-Hypnotic DrugsSedative-Hypnotic Drugs

BenzodiazepinesBenzodiazepinesBarbituratesBarbituratesOthersOthers

Sedatives Sedatives （镇静药）：（镇静药）：

能缓和激动，消除躁动，恢复安静情绪的药物能缓和激动，消除躁动，恢复安静情绪的药物

Hypnotics Hypnotics （催眠药）：（催眠药）：

能促进和维持近似生理睡眠的药物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，故合称为等中枢抑制作用，故合称为镇静催眠药镇静催眠药（（ sedsedative-hypnoticsative-hypnotics ））

Circadian rhythms of Circadian rhythms of physiological functions:physiological functions:

different functions in the different functions in the waking and sleepingwaking and sleeping

Enhanced alertnessEnhanced alertness

Phases of the sleepingPhases of the sleeping

A.A. Benzodiazepines Benzodiazepines

Diazepam Diazepam 地西泮地西泮（安定）（安定）

N

NCl

CH3

O

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

(2) Sedative-hypnotic effects(2) Sedative-hypnotic effects at relatively larger doses, no anesthetic effect; at relatively larger doses, no anesthetic effect; not remarkably affect on REMnot remarkably affect on REM used for used for insomniainsomnia and and preanesthetic medicationpreanesthetic medication

A.A. Benzodiazepines Benzodiazepines

(3) Antiepileptic and anticonvulsant effects(3) Antiepileptic and anticonvulsant effects convulsion due various causes; status epilepticusconvulsion due various causes; status 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 increrelaxing the spasticity of skeletal muscle, probably by incre

asing presynaptic inhibition in the spinal cord.asing 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

2. 2. Mechanisms of actionsMechanisms of actions

(1) Sites of action:(1) Sites of action: mainly acts on mainly acts on limbic systemlimbic system and and midbmidbrain reticular formationrain reticular formation..

(2) Interaction with GABA(2) Interaction with GABAAA receptor receptor Benzodiazepines bind to specific, high affinity sites on the ceBenzodiazepines bind to specific, high affinity sites on the ce

ll membrane, which are separate from but adjacent to the rell membrane, which are separate from but adjacent to the receptor for ceptor for -aminobutyric acid (GABA). -aminobutyric acid (GABA).

The binding of benzodiazepines The binding of benzodiazepines enhances the affinity of GABA receptor enhances the affinity of GABA receptor for this neurotransmitterfor this neurotransmitter, resulting in a more frequent opening of adjac, resulting in a more frequent opening of adjacent chloride channels. ent chloride channels. - - coagonistcoagonist

This in turn results in This in turn results in enhanced hyperpolarizationenhanced hyperpolarization （（超极化超极化）） and furtand further inhibition of neuronal firing.her inhibition of neuronal firing.

A.A. Benzodiazepines Benzodiazepines

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

Action of the central iAction of the central inhibitory transmitter nhibitory transmitter GABA on ClGABA on Cl-- influx a influx and the action sites of bnd the action sites of benzodiazepines (BDZenzodiazepines (BDZs)s)

GABAGABA

BDZsBDZs

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

ACh ACh NE NE

DA DA 5-HT 5-HT

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

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

3. 3. Adverse effectsAdverse effects

(1) Central depression(1) Central depression Most common:Most common: drowsiness and confusion ( drowsiness and confusion (potentiated by ethpotentiated by eth

anol or other central depressantsanol or other central depressants)) Ataxia; cognitive impairmentAtaxia; cognitive impairmentAntagonized by BZ receptor antagonistAntagonized by BZ receptor antagonist flumazenil flumazenil

（氟马西尼）（氟马西尼）

(2) Tolerance and dependence(2) Tolerance and dependence Withdrawal syndrome: central excitation Withdrawal syndrome: central excitation

A.A. Benzodiazepines Benzodiazepines

(3) Others(3) Others local pain, respiratory and CVS reactions local pain, respiratory and CVS reactions (i.v.)(i.v.) teratogenic effectsteratogenic effects

(4) Contraindications(4) Contraindications Myasthenia gravisMyasthenia gravis Infants < 6 monthsInfants < 6 months Pregnancy and lactation mothersPregnancy and lactation mothers Elderly, heart/lung/liver/kidney dysfunctionElderly, heart/lung/liver/kidney dysfunction Fine motor coordinationFine motor coordination

A.A. Benzodiazepines Benzodiazepines

Other benzodiazepinesOther benzodiazepines

According to the metabolismsAccording to the metabolisms

Long-actingLong-acting ：： diazepamdiazepam, chlordiazepoxide (, chlordiazepoxide ( 氯氮卓氯氮卓 ), flurazepam (), flurazepam ( 氟西泮氟西泮 ))

Intermediate-actingIntermediate-acting ：： Nitrozepam (Nitrozepam ( 硝西泮硝西泮 ), flunitrozepam (), flunitrozepam ( 氯硝西泮氯硝西泮 ), ), oxazepam (oxazepam ( 奥沙西泮奥沙西泮 ), estazolam (), estazolam ( 艾司唑仑艾司唑仑））

Short-actingShort-acting ：： triazolam (triazolam ( 三唑仑三唑仑 ))

A.A. Benzodiazepines Benzodiazepines

艹

Phenobarbital Phenobarbital 苯巴比妥苯巴比妥

C2H5

CO

NH

NH

CO

CO

C

C6H5

B.B. Barbiturates Barbiturates

1. 1. ADMEADME Inducing hepatic enzymesInducing hepatic enzymes Alkalining urine: excretion Alkalining urine: excretion

2. 2. Pharmacological effects and clinical usesPharmacological effects and clinical uses

(1) Sedative-hypnotic effects(1) Sedative-hypnotic effects

(2) Preanesthetic medication(2) Preanesthetic medication

(3) Antiepileptic and anticonvulsant effects(3) Antiepileptic and anticonvulsant effects

B.B. Barbiturates Barbiturates

3. 3. Adverse effectsAdverse effects

(1) Central depression:(1) Central depression: including after effectincluding after effect

(2) Tolerance and dependence:(2) Tolerance and dependence: long-term useslong-term uses

(3) Acute poisoning(3) Acute poisoning supporting therapiessupporting therapies alkalizing urinealkalizing urine hemodialysishemodialysis

B.B. Barbiturates Barbiturates

Chloral hydrate Chloral hydrate 水合氯醛水合氯醛 Sedative-hypnotic effectsSedative-hypnotic effectsAnticonvulsant effect:Anticonvulsant effect: usually used in childrenusually used in children

Hydroxyzine Hydroxyzine 羟嗪（安泰乐）羟嗪（安泰乐）

Meprobamate Meprobamate 甲丙氨酯（眠而通）甲丙氨酯（眠而通）

BuspironeBuspirone 丁螺环酮丁螺环酮

MethaqualoneMethaqualone 甲喹酮（安眠酮）甲喹酮（安眠酮）

C.C. Others Others

Antihistamines Antihistamines 抗组胺药抗组胺药

Ethanol Ethanol 乙醇乙醇

Melatonin Melatonin 褪黑素褪黑素

C.C. Others Others

Part 8Part 8

Central stimulantsCentral stimulants

Psychomotor stimulantsPsychomotor stimulantsRespiratory center stimulantsRespiratory center stimulants

D.D. Central stimulants Central stimulants

Psychomotor stimulantsPsychomotor stimulants

(mainly acting on cerebral cortex)(mainly acting on cerebral cortex)

Xanthines:Xanthines: caffeine caffeine 咖啡因咖啡因

Related drugsRelated drugs

Respiratory center stimulantsRespiratory center stimulantsDirect stimulationDirect stimulation

Indirect stimulation (reflex)Indirect stimulation (reflex)

A A Psychomotor stimulants Psychomotor stimulants

Caffeine Caffeine 咖啡因咖啡因

N

N N

N

H3C CH3�

CH3�

O

O

A A Psychomotor stimulants Psychomotor stimulants

1. 1. Pharmacological effectsPharmacological effects

(1) Central stimulation(1) Central stimulation

(2) CVS effects:(2) CVS effects: cardiac stimulation, dilatation of vesselscardiac stimulation, dilatation of vessels

(3) Relaxing smooth muscles:(3) Relaxing smooth muscles: airways, GIairways, GI

(4) Other effects:(4) Other effects: Gastric acid secretion, diuretic effectGastric acid secretion, diuretic effect

(5) Mechanisms of action(5) Mechanisms of action ：： inhibiting PDE- cAMP inhibiting PDE- cAMP ；；antagonizing Aantagonizing A11 adenosine receptor & GABA receptor adenosine receptor & GABA receptor

A A Psychomotor stimulants Psychomotor stimulants

2. 2. Clinical usesClinical usesCentral depressionCentral depressionAdjuvant of migraine and antipyretic-analgesic Adjuvant of migraine and antipyretic-analgesic

drugsdrugs

3. 3. Adverse effectsAdverse effectsCentral excitationCentral excitationConvulsion (overdose)Convulsion (overdose)

A A Psychomotor stimulants Psychomotor stimulants

Methylphenidate Methylphenidate 哌甲酯（利他灵）哌甲酯（利他灵）

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; e; enuresis; nuresis; etc.etc.

Meclofenoxate Meclofenoxate 甲氯芬酯（氯酯醒）甲氯芬酯（氯酯醒）

Adjuvant of central depressive diseases; enuresiAdjuvant of central depressive diseases; enuresis; s; 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 effectsDirect Direct (respiratory centre)(respiratory centre) and indirect and indirect (reflex via (reflex via

chemoreceptor)chemoreceptor) stimulation stimulation

2. 2. Clinical usesClinical usesRespiratory failureRespiratory failure

3. 3. Adverse effectsAdverse effectsElevation of BP, tachycardia, tremor, convulsionElevation of BP, tachycardia, tremor, convulsion

Dimefline Dimefline 二甲弗林 （回苏灵）二甲弗林 （回苏灵）

Direct stimulationDirect stimulation

LobelineLobeline 洛贝林（山梗菜碱）洛贝林（山梗菜碱）

Indirect stimulationIndirect stimulation

B B Respiratory center stimulants Respiratory center stimulants