NERVOUS

SYSTEM

Leeland Anthony L. dela Luna,

Pharm.D, R.Ph

NEURON 1

Synapse

Synapse

NEURON 3

NEURON 2
Synapse

NERVE IMPULSE

PRESYNAPSE

Vesicles

Containing
Neurotransmitters

NT are released
through Exocytosis

SYNAPSE

Receptors
When NT binds to
its receptors, it
activates channels
to produce another
Nerve Impulse

NERVE IMPULSE
POSTSYNAPSE

How are NT Terminated?

PRESYNAPSE

3. Reuptake
2. Metabolism
COMT or MAO
1. Diffuse &
Degrade

SYNAPSE

Leaving the
synapse free from
stimulation

POSTSYNAPSE

The Monoamines

THE MONOAMINES
Metabolized by MAO enzymes
NOREPINEPHRINE (NE)

Energy = Adrenalin
Rush!!!

Excitatory transmitter of the brain and smooth

muscles
Dopamine = Desire

DOPAMINE (Dopa)

Receptors are D1 and D2 (brain)

SEROTONIN (SE, 5-HT)

50% in the GIT

5HT = Temp.
(Hyperthermia) or
induce sleep
5HT = Mood
(Depression)
90% in the GIT

Released from inhibitory neurons

Stimulates either 5-HT1 or 5-HT2 receptors

Biosynhesis & Metabolism of Dopamine

Biosynthesis

Tyrosine

Dopamine

Metabolism

Tyrosine hydroxylase
MAO

COMT

DOPA
3-methoxytyramine

ALAAD
Dopamine

Dihydroxyphenylacetic acid

Homovanillic acid

Biosynthesis & Metabolism of NE

Tyrosine

Biosynthesis
Tyrosine hydroxylase

NE

Metabolism

MAO
MAO

DOPA
ALAAD

Dihydroxymandelic
acid
Dopamine

Dopamine -hydroxylase
(Sympathetic nerve)

MAO

NE
3-methoxy-4-hydroxy-mandelic acid

Phenethanolamine-Nmethyltransferase
(Adrenal medulla)

Normetanephrine

EPI

Neurotransmitters
GABA Gamma Amino Butyric Acid
Inhibitory neurotransmitter of the brain
Binds to either GABAA or GABAB

EAA Excitatory Amino Acid

Glutamate or structurally similar chemical
Stimulates EAA receptors
Thought to be important in learning, memory and
other brain functions

Neurotransmitters
The Opioids
Endorphins, enkephalins and dynorphins are
opiate receptor agonists
In times of stress and pain, endogenous peptides
act at opiate receptors (to relieve pain)

Other neuropeptides
Substance P
VIP (Vasoactive Intestinal Peptides)

AUTONOMIC NERVOUS SYSTEM

Anatomical Differences of Peripheral Nervous System

Autonomic Nervous System

Sympathetic

preganglionic

postganglionic

Parasympathetic

Somatic Nervous System

Enteric Nervous System

Consists of the submucosal, myenteric, and
subserosal plexuses
Parasympathetic stimulation activates ENS
Sympathetic stimulation inhibits ENS

Dilation of Pupils
(Mydriasis)
Widening of mouth +
Salivation
Heart beat (+) Inotropic &
Chronotropic
Bronchodilation
GIT Activity

Muscle Tone
Bladder Relaxation =
Urination
Piloerection

Fight or Flight

Adrenergic Nervous System Fight or Flight

Catabolic
Functional entity
Diffuse type
Discharge as a complete
system

Constriction of Pupils
(Myosis)
Salivation
Heart beat (-) Inotropic &
Chronotropic
Bronchoconstriction
GIT Activity

Bladder Contraction =
Urination

Rest & Digest

Essential for Life

Anabolic
Unfunctional entity
Discrete
Never discharge as
complete system

Cholinergic Nervous System Rest and Digest

cranial

THORACOLUMBAR

CRANIOSACRAL

cervical

thoracic

lumbar

sacral

CHOLINERGIC RECEPTORS

ACETYLCHOLINE RECEPTORS
NICOTINIC and MUSCARINIC
Nicotinic
subtypes are:
NN (neuronal)
NM (muscular)

Directly coupled to cation-channels

Mediate fast excitatory synaptic transmission at the
neuromuscular junction (NMJ), autonomic ganglia, and at
various sites in the CNS

MUSCARINIC RECEPTORS (mAchRs)

G-protein coupled receptors causing:
Activation of phospholipase C (IP3 and DAG as
second messengers)
Inhibition of adenylate cyclase
Activation of K+-channels or inhibition of Ca+2channels

Mediate Ach effects at postganglionic

parasympathetic synapses (mainly heart,
smooth muscle, glands), and contribute to
ganglionic excitation.

MIOSIS CILLIARY
MUSCLE contraction
ACCOMODATION
GLAND
SECRETION
= Lacrimation,
Salivation &
Sweating

M3

M1

SLOW excitation of
ganglia :
DEPOLARIZATION

M3
M3

HR & CONDUCTION VELOCITY

(-) Chronotrpoic (SA node)
M2
(-) Dromotropic (AV node)

BRONCHOSPASM
Secretion of mucus
Bronchoconstriction
(Slow deep breaths)

INHIBITORY!!! (Gi - G PROTEIN)

M3
PERISTALSIS
GI Secretions

M3

MUSCARINIC
RECEPTORS

VASODILATION
release of NO =
PR = BP

M3

BLADDER
CONTRACTION
= Voiding

NN

NM

NICOTINIC
RECEPTORS

FAST excitation of
ganglia :
DEPOLARIZATION
N = Neuronal

MUSCLE CONTRACTION
Found In Skeletal muscles
M = Muscles

ADRENERGIC RECEPTORS

ADRENERGIC RECEPTORS
Main classification: - and - subtypes (all are
G-protein coupled receptors)
Two -adrenoceptor subtypes: 1, 2
1-receptors activate phospholipase C, thus
producing IP3 and DAG
2 receptors inhibit adenylate cyclase. Thus
decreasing cAMP formation

Three - adrenoceptor subtypes: 1,2,3

All types of -receptor stimulate adenylate
cyclase, thus increasing cAMP formation

The Alpha Receptors

1
PILOERECTION
Goosebumps

1
GLYCOGENOLYSIS &
GLUCONEOGENESIS
SUGAR = ENERGY

2
INHIBIT INSULIN RELEASE
INSULIN = SUGAR

MYDRIASIS
RADIAL MUSCLE
contraction

1
CONSTRICTION of
ARTERIES = PR = BP

2
DILATION of ARTERIES =
PR = BP

2
INHIBITS NE RELEASE
NE = BP

Effects of alpha 1 receptor activation

on different tissues and systems

Postsynaptic Alpha1 Receptors on Vascular

Smooth Muscle

Presynaptic Alpha2 Receptors

Alpha2 receptors also exist presynaptically associated
with nerve terminals
Activation of these receptors inhibits the release of NE
NE acts at presynaptic alpha2 receptors to inhibit its own
release.

Alpha-2 receptor activation

Drugs affecting alpha receptors

LIPOLYSIS

BRONCHODILATION
Bronchioles relax
(fast shallow
breaths)

UPTAKE OF K in Muscles
K levels in blood =
HYPOKALEMIA

2
2

GLUCONEOGENESIS &
GLYCOGENOLYSIS
Sugar levels = ENERGY

(+) Chronotropy &

(+) Inotropy
HR & Force of
Pumping

1
RENIN PRODUCTION
= PR = BP
(Juxtaglomerular Cells)

URINARY RETENTION
GI MOTILITY
Bladder relaxation (GU)
Constipation (GIT)

UTERINE RELAXATION

Effect of Beta1 Receptor Activation

on the Heart

Effect of Beta2 Receptor Activation

on Smooth Muscle
Leads to vascular and
nonvascular smooth muscle
relaxation
Drugs that activate the
beta2 receptor can be;
used to treat as asthma
(by relaxing airway smooth
muscle) and
premature labor (by relaxing
uterine smooth muscle).

USES OF SELECTIVE BETA2 AGONISTS

1. Airways dysfunction; bronchial asthma,
chronic bronchitis, emphysema

In airways dysfunction, beta2 selective agonists relax airways

thus decreasing airways resistance

2. Premature labor

In premature labor, the beta2 selective agonists relax uterine

smooth muscle.
Drugs that relax uterine smooth muscle are referred to as
tocolytic agents

The Beta receptors

Main effects of ADRENERGIC receptor

Activation
Type of
Receptor

Locations

Effects

Radial muscle of the iris

Arteriolar smooth muscle
GI and GU sphincters
Pilomotor smooth muscle
Seminal vesicle smooth
muscle
liver

Pupillary dilation (contraction)

Incr PR and BP (contraction)
Retention (contraction)
Piloerection (contraction)
Ejaculation (contraction)
Glycogenolysis and
gluconeogenesis

Presynaptic nerve
terminals

Inhibits release of NE
(presynaptic inhibition)

Platelets
Pancreatic cells

Aggregation
Inhibits insulin release
(hyperglycemia)

Main effects of ADRENERGIC receptor

Activation
Type of
Receptor
1

Locations
Heart

Juxtaglomerular cells
2

Vascular smooth muscle

Bronchiolar smooth muscle
GI and urinary bladder
smooth muscle
Uterine smooth muscle
Skeletal muscle
Liver

Adipose tissue

Effects
Incr in heart rate, contractility
and conduction
Incr in secretion of renin (incr
BP)
Vasodilation (relaxation)
Bronchodilation (relaxation)
Decr GI and GU motility
(relaxation)
Decr uterine contraction
(relaxation)
Uptake of K+ in skeletal muscles
Glycogenolysis &
gluconeogenesis
Lipolysis