Transcript 中枢神经系统药理学

Drugs for Central Nervous System
Department of Pharmacology
Yunyang Medical College
Wanhong Zhao (赵万红)
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Chapter 12 General Theory for Central
Nervous System Pharmacology
Objectives and Requirements
 Understanding the metabolic processes and
physiological functions of central
neurotransmitters and their receptors
 Understanding the categories and
characteristics of the drugs for CNS
CNS: primary conduction and coordination
Modes: nerve and/or humoral regulation
for maintaining homeostasis and producing
response for external environment
Humans:
dominating
complicated behaviors
intellect
and
Section 1 Cytologic Basis of CNS
1.Nerve cell
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Cell body, dendrite and axon
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Inclusion body in cytoplasm: pyknotic body(致
密小体) and lipofuscin(脂褐素) etc.
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Basic structure and function unit of CNS
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Major function: transmitting message
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Synapse is the centre of transmitting message
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
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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
information 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
internal organ activities etc
Excitatory transmitter, e.g. ACh is released in brain
when an animal is infuriated and it is reduced when an
animal 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
insufficiency of cerebral cortex in epileptics may
cause convulsion; valproate sodium can treat
various kinds of epileptic 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
former three are ligand-gated ion channel and the final
impacts phosphatidylinositol metabolism and adenylcyclase
activity
 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)
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Concentrated distribution in CNS, e.g. in hypothalamus
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Receptors: α and β
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Functions: alertness, sleep and emotion etc; e.g. when
NA neuron activity increases, happiness and agitation
appear.
5. Dopamine (DA)
Distribution : relative centered; clear projection pathways;
centered in striatum (ST, 纹状体), nigra (SN) and globus
pallidus (苍白球)
①SN－ST pathway：advanced center of the motion function in
extrapyramidal system; function ↓→PD, function ↑→minimal
brain dysfunction (多动症)
②Mes－limbic system: emotion and affection
③Mes－cortex pathway: cognition, thinking, sensation and
senses
④Tuberculum-funnel pathway：regulating endocrine function
of antehypophysis (垂体前叶)
 Receptors: D1 and D2; five subtypes D1-5; the
pharmacological characteristics of D1 and D5 are
similar 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
system and Mes-cortex pathways causes
schizophrenia; treatment—DA antagonists
6. 5－Hydroxytryptamine (5－HT)
 Distribution: similar to that of NA
 5-HT transporter is the main target of antidepressants,
which participates the regulations of cardiovascular
activity, sleep, algesia, affection and endocrine
 Functions: inhibition and stabilization
7. Histamine (H)
 Maldistribution; more in hypothalamus and reticular
formation (网状结构), H1, H2 and H3 receptor
 Functions: regulating psychoactivity, decreasing body
temperature, participating drinking and causing vomit;
exciting 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, hypnosis, preventing cough and inhibiting
respiration function etc.
9. Prostaglandin (PG)
 Uniformity distribution, many can induce fever and the
effect of PGE2 is the strongest.
 Central PG synthetase (cycloxygenase) inhibitors, e.g.
acetyl salicylic 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
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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
evolution. Hypotension and respiratory failure appear when
brain is inhibited severely.
Drugs can impact some functions of CNS selectively, e.g.
analgesia and antipsychotic etc.
Action modes of CNS drugs
Most of drugs impact some courses of synaptic
transmission, so cause some homologous function changes,
e.g. synthesis, storage, release and deactivation of
transmitter, and exciting or blocking receptor etc.
Minority impact the energy metabolism or membrane
stability---no specific detoxicant, e.g. general anesthetics.
Review Subjects
1.
To compare the characteristics of neurotransmitter,
neuromodulator and neurohormone.
2.
To state pharmacological features of CNS.