INTRODUCTION TO CNS
PHARMACOLOGY
Anita Q. Sangalang, MD, FPOGS
FACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
CNS PHARMACOLOGY
Most
drugs that act on the CNS do so by
changing ion flow through transmembrane
channels of nerve cells
CNS PHARMACOLOGY
2 MAJOR TYPES OF ION CHANNEL
VOLTAGE-GATED ION CHANNELS
Respond to changes in membrane potential
Concentrated on the axons of nerve cells
CNS PHARMACOLOGY
2 MAJOR TYPES OF ION CHANNEL
VOLTAGE-GATED ION CHANNELS
Include the sodium channels responsible
for action potential propagation
Cell bodies and dendrites also have voltage-
sensitive ion channels for potassium and
calcium
CNS PHARMACOLOGY
2 MAJOR TYPES OF ION CHANNEL
LIGAND-GATED ION CHANNELS
Chemically-gated
Respond to chemical neurotransmitters
(NTAs) that bind to receptor subunits of
the channel
CNS PHARMACOLOGY
2 MAJOR TYPES OF ION CHANNEL
LIGAND-GATED ION CHANNELS
NTAs also bind to G protein-coupled
receptors (metabotropic receptors)
Found on all cell bodies and on both
the presynaptic and postsynaptic sides
of the synapses
CNS PHARMACOLOGY
TYPES OF RECEPTOR-CHANNEL COUPLING
1. Through a receptor that acts directly on
the channel protein
2. Through a receptor that is coupled to the
ion channel through a G protein
CNS PHARMACOLOGY
TYPES OF RECEPTOR-CHANNEL COUPLING
2. Through a receptor coupled to a G protein
that modulates the formation of diffusible
second messengers
Cyclic AMP
Inositol triphosphate (IP3)
Diacylglycerol (DAG)
CNS PHARMACOLOGY
ROLE OF THE ION CURRENT CARRIED BY
THE CHANNEL
SYNAPSE- communication
EPSPs
IPSPs
CNS PHARMACOLOGY
EXCITATORY POSTSYNAPTIC POTENTIALS
(EPSPs)
Depolarizing potential change
Generated by
Opening of sodium or calcium channels
Closing of potassium channels
CNS PHARMACOLOGY
EXCITATORY POSTSYNAPTIC POTENTIALS
(EPSPs)
Na+, K+, Ca+2
-70 mV
CNS PHARMACOLOGY
INHIBITORY POSTSYNAPTIC POTENTIALS
(IPSPs)
Hyperpolarizing potential change
Generated by
Opening of potassium or chloride channels
CNS PHARMACOLOGY
INHIBITORY POSTSYNAPTIC POTENTIALS
(IPSPs)
K+ , Cl- at the postsynaptic , Ca+2 at the
presynaptic
-70 mV
CNS PHARMACOLOGY
SITES AND MECHANISMS OF DRUG ACTION
Some drugs exert their effect through direct
interactions with molecular components of
ion channels on axons
Carbamazepine
Phenytoin
Local anesthetics and some drugs used
for general anesthesia
CNS PHARMACOLOGY
SITES AND MECHANISMS OF DRUG ACTION
Mostdrugs exert their effect mainly at the
synapses
CNS PHARMACOLOGY
SITES AND MECHANISMS OF DRUG ACTION
May act presynaptically to alter
Synthesis
Storage
Release
Reuptake
Metabolism of transmitter chemicals
CNS PHARMACOLOGY
SITES AND MECHANISMS OF DRUG ACTION
Activate or block
Pre- and postsynaptic receptors for specific
transmitters
Interfere with the action of second
messengers
CNS PHARMACOLOGY
SITES AND MECHANISMS OF DRUG ACTION
Parachlorophenylalanine
Inhibits synthesis of serotonin
Reserpine
Inhibits storage of cathecolamines
CNS PHARMACOLOGY
SITES AND MECHANISMS OF DRUG ACTION
Amphetamine
Inhibits release of catecholamines
Anticholinesterase
Inhibits degradation of cathecolamines
CNS PHARMACOLOGY
CNS ORGANIZATION
2 TYPES OF NEURONAL SYSTEM
A. HIERARCHICAL SYSTEM
Contain large myelinated, rapidly conducting
fibers
Control major sensory and motor functions
Excitability of the CNS
CNS PHARMACOLOGY
CNS ORGANIZATION
2 TYPES OF NEURONAL SYSTEM
A. HIERARCHICAL SYSTEM
Major excitatory transmitters
Aspartate
Glutamate
CNS PHARMACOLOGY
CNS ORGANIZATION
2 TYPES OF NEURONAL SYSTEM
A. HIERARCHICAL SYSTEM
Also include numerous small inhibitory
interneurons transmitter
Gamma amino butyric acid (GABA)
Glycine
CNS PHARMACOLOGY
CNS ORGANIZATION
2 TYPES OF NEURONAL SYSTEM
B. DIFFUSED/NON-SPECIFIC NEURONAL
SYSTEM
Broadly distributed, with single cells
frequently sending processes to many
different parts of the brain-tangential
CNS PHARMACOLOGY
CNS ORGANIZATION
2 TYPES OF NEURONAL SYSTEM
B. DIFFUSED/NON-SPECIFIC NEURONAL
SYSTEM
Varicosities
Periodic enlargements that contain
transmitter vesicles
Located in the axons
CNS PHARMACOLOGY
CNS ORGANIZATION
2 TYPES OF NEURONAL SYSTEM
B. DIFFUSED/NON-SPECIFIC NEURONAL
SYSTEM
Transmitters
Amines (NE, dopamine and serotonin)
Peptides that act on metabotropic
receptors
CNS PHARMACOLOGY
CNS ORGANIZATION
2 TYPES OF NEURONAL SYSTEM
B. DIFFUSED/NON-SPECIFIC
NEURONAL SYSTEM
Marked effects on CNS functions
Attention
Appetite
Emotional states
CNS PHARMACOLOGY
CRITERIA FOR TRANSMITTER STATUS
1. Present in higher concentration in the
synaptic area than in other areas
(localized in appropriate areas)
CNS PHARMACOLOGY
CRITERIA FOR TRANSMITTER STATUS
2. Released by electrical or chemical
stimulation via a calcium-dependent
mechanism
CNS PHARMACOLOGY
CRITERIA FOR TRANSMITTER STATUS
3. Synaptic mimicry
Produce the same sort of postsynaptic
response that is seen with physiologic
activation of the synapse
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS (Table in Katzung)
ACETYLCHOLINE (Ach)
5% of neurons have receptors for Ach
G protein-coupled muscarinic M1 receptors
Slow excitation
Decrease permeability to potassium
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
DOPAMINE
Inhibitory actions at synapses in specific
neuronal systems
G protein-coupled activation of K+ channels
D2 receptor is the main dopamine subtype
Increase cAMP
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
NOREPINEPHRINE
Excitatory effects
Activation of 1 and 1 receptors
Decrease K+ conductance
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
NOREPINEPHRINE
Inhibitory effects
Activation of 2 and 2 receptors
Increase K+ conductance
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
SEROTONIN
Multiple 5 hydroxytryptamine (5-HT)
receptor subtypes
Metabotropic
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
SEROTONIN
Inhibitory at many CNS sites
Excitatory depending on the receptor subtype
activated
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
GLUTAMIC ACID
Excitatory for most neurons
N-methyl-D-aspartate (NMDA) receptor
Learning and memory
Inhibition of adenyl cyclase
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
GABA AND GLYCINE
GABA is the primary NTA mediating IPSPs
GABAA receptor activation
Opens Cl- conductance
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
GABA AND GLYCINE
GABAB receptor activation
Opens K+ channels
Closes Ca+2 channels
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
GABA AND GLYCINE
Glycine is more numerous in the cord
Glycine is inhibitory
Increases Cl- conductance
CNS PHARMACOLOGY
CHEMICALS ACCEPTED AS NTAs IN THE
CNS
OPIOID PEPTIDES
Beta-endorphins, dynorphins
Inhibitory (presynaptic)
Decrease Ca+2 conductance
Inhibitory (postsynaptic)
Increase K+ conductance
