department of pharmacology yunyang medical college
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Drugs for Central Nervous System. Department of Pharmacology Yunyang Medical College. Wanhong Zhao ( 赵万红 ). Mailbox for Answering Questions Website : Homepage of campus net/Teaching resources/Construction platform of excellent courses/Constructing courses/Pharmacology [email protected] - PowerPoint PPT PresentationTRANSCRIPT
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 [email protected] [email protected]
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.