Department of PharmacologyYunyang Medical College

Drugs for Central Nervous System

Wanhong Zhao ( 赵万红 )

Mailbox for Answering Questions Website ： Homepage of campus net/Teaching resources/Construction platform of excellent courses/Constructing courses/Pharmacology yymcyaoli@163.com zhaowanhong0803@163.com

Chapter 12 General Theory for

Central Nervous System

Pharmacology

Understanding the metabolic processes and physiological functions of central neurotransmitters and their receptors Understanding the categories and characteristics of the drugs for CNS

Objectives and Requirements

CNS: primary conduction and coordination

Modes: nerve and/or humoral regulation for maintaining homeostasis and producing response for external environment

Humans: dominating intellect and complicated behaviors

1.Nerve cell● Cell body, dendrite and axon● Inclusion body in cytoplasm: pyknotic body( 致

密小体 ) and lipofuscin( 脂褐素 ) etc.● Basic structure and function unit of CNS● Major function: transmitting message● Synapse is the centre of transmitting message

Section 1 Cytologic Basis of CNS

2. Neuroglia

Astrocyte, oligodendrocyte and microglia Functions ： support, insulation, homeostasis, guiding the growth of neuron, and participating the deactivation of transmitter and nerve regeneration etc.

3. Neuronal circuit

Neuron regulation is performed by

neuronal circuit (not only one

neuron)

Messages are processed and

integrated by neuron circuit

4. Synapse and message transmission

Synapse composition: presynaptic membrane, postsynaptic membrane and synaptic cleft Synapse categories: chemical, electric and mixed Synaptic transmission: synthesis and storage of transmitter, depolarization of presynaptic membrane and extracellular calcium influx triggering transmitter release, combination of transmitter and receptor producing biological effect, and transmitter elimination and recycle to vesicle Message may be transmitted by two way at synapse

Section 2 Transmitters and

Receptors of CNS

Neurotransmitter: transmitting signal quickly, strong action and high selectivity

Neuromodulator ： no transmitter action, modulating transmitter releasing and the excitability of postsynaptic cell; its effects are chronic, long and extensive

Neurohormone: being mainly neuropeptides Several transmitters and modulators may coexist

in one nerve terminal Some neurotrophic and cellular factors impact i

nformation transfer by regulating gene expression

We have known more than 30 transmitters.

1. Acetylcholine (ACh)

Distribution: widespread in CNS

Receptors: M (especially M1) and N

Functions: involving in motion, memory, alertness and i

nternal organ activities etc

Excitatory transmitter, e.g. ACh is released in brain wh

en an animal is infuriated and it is reduced when an anim

al sleeps

2. γ-aminobutyric acid (GABA)

Widespread and non-uniform in brain, especially in

nigra ( 黑质 ) and globus pallidus ( 苍白球 )

Receptors: A, B and C, especially A type in brain

Inhibitive transmitter in CNS, e.g. GABA insufficie

ncy of cerebral cortex in epileptics may cause convu

lsion; valproate sodium can treat various kinds of e

pileptic seizures because it inhibits the degradation

of GABA

3. Excitatory Amino Acids (EAA)

Glu and asp: the maximal content amino acid in mammal’

brain

Receptors: NMDA, AMPA, KA and metabotropic; the for

mer three are ligand-gated ion channel and the final impact

s phosphatidylinositol metabolism and adenylcyclase activit

y

NMDA receptor is the target of many nervous and mental

disorders

EAA are related with study and memory, neuron plasticity,

epilepsy and CNS degenerative diseases

4. Noradrenaline (NA)

Concentrated distribution in CNS, e.g. in hypothalamus

Receptors: α and β

Functions: alertness, sleep and emotion etc; e.g. when N

A neuron activity increases, happiness and agitation app

ear.

5. Dopamine (DA)

Distribution : relative centered; clear projection pathways; cent

ered in striatum (ST, 纹状体 ), nigra (SN) and globus pallidu

s ( 苍白球 )

①SN － ST pathway ： advanced center of the motion function

in extrapyramidal system; function ↓→PD, function ↑→mi

nimal brain dysfunction (多动症 )

②Mes － limbic system: emotion and affection

③Mes － cortex pathway: cognition, thinking, sensation and sen

ses

④Tuberculum-funnel pathway ： regulating endocrine function

of antehypophysis ( 垂体前叶 )

Receptors: D1 and D2; five subtypes D1-5; the pha

rmacological characteristics of D1 and D5 are simila

r to that of D1, which are called D1-like receptors ，

the other—D2-like receptors

Relations with diseases ： SN-ST pathway ↓→PD; treatment—supplement

DA or DA receptor agonists

Hyperfunction of D2-like receptor in Mes-limbic s

ystem and Mes-cortex pathways causes schizophre

nia; treatment—DA antagonists

6. 5 － Hydroxytryptamine (5 － HT) Distribution: similar to that of NA 5-HT transporter is the main target of antidepressants, w

hich participates the regulations of cardiovascular activit

y, sleep, algesia, affection and endocrine Functions: inhibition and stabilization

7. Histamine (H) Maldistribution; more in hypothalamus and reticular for

mation ( 网状结构 ), H1, H2 and H3 receptor Functions: regulating psychoactivity, decreasing body te

mperature, participating drinking and causing vomit; exc

iting H1→excitation, exciting H2→inhibition; the lethargy

effect of antihistamine drugs may involve in H1 blockage

8. Endopioid Peptide

More in ST and HT ( 下丘脑 )

Opium (the main active component is morphine) has sedative, hypno

sis, preventing cough and inhibiting respiration function etc.

9. Prostaglandin (PG)

Uniformity distribution, many can induce fever and the effect of PG

E2 is the strongest.

Central PG synthetase (cycloxygenase) inhibitors, e.g. acetyl salicyli

c acid reduces PG so that it has antipyretic action

Section 3 Pharmacological characteristics of CNS

Excitation: mild to severe—euphoria, insomnia, discomfort, illusion, dilusion ( 妄想 ), mania and convulsion etc.

Inhibition: sedative, hypnotic, depression, anesthesia and coma etc.

Drug categories: central stimulants and depressants

Inhibition function is more sensitive to drugs than excitation

Sensitivity Differences of Brain Tissue to drugs

High evolutive brain tissues have more sensitivity for drugs,

e.g. cortex. Vital center in medulla oblongata is lower evolutio

n. Hypotension and respiratory failure appear when brain is i

nhibited severely.

Drugs can impact some functions of CNS selectively, e.g. ana

lgesia and antipsychotic etc.

Action modes of CNS drugs

Most of drugs impact some courses of synaptic transmiss

ion, so cause some homologous function changes, e.g. synt

hesis, storage, release and deactivation of transmitter, and

exciting or blocking receptor etc.

Minority impact the energy metabolism or membrane st

ability---no specific detoxicant, e.g. general anesthetics.

Review Subjects

1. To compare the characteristics of neurotransmitter, neu

romodulator and neurohormone.

2. To state pharmacological features of CNS.