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NERVOUS

SYSTEM

NERVOUS SYSTEM Leeland Anthony L. dela Luna, Pharm.D, R.Ph

Leeland Anthony L. dela Luna, Pharm.D, R.Ph

Synapse NEURON 3 Synapse NEURON 1 Synapse NEURON 2

Synapse

NEURON 3

Synapse NEURON 3 Synapse NEURON 1 Synapse NEURON 2
Synapse NEURON 3 Synapse NEURON 1 Synapse NEURON 2

Synapse

NEURON 1

Synapse NEURON 3 Synapse NEURON 1 Synapse NEURON 2
Synapse NEURON 3 Synapse NEURON 1 Synapse NEURON 2

Synapse

NEURON 2

NERVE IMPULSE
NERVE IMPULSE

PRESYNAPSE

Vesicles

Containing

Neurotransmitters

NT are released through Exocytosis

SYNAPSE

NERVE IMPULSE
NERVE IMPULSE

Receptors

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

POSTSYNAPSE

How are NT Terminated? PRESYNAPSE 3. Reuptake 2. Metabolism COMT or MAO SYNAPSE 1. Diffuse

How are NT Terminated?

PRESYNAPSE

How are NT Terminated? PRESYNAPSE 3. Reuptake 2. Metabolism COMT or MAO SYNAPSE 1. Diffuse &
How are NT Terminated? PRESYNAPSE 3. Reuptake 2. Metabolism COMT or MAO SYNAPSE 1. Diffuse &

3. Reuptake

2. Metabolism COMT or MAO

PRESYNAPSE 3. Reuptake 2. Metabolism COMT or MAO SYNAPSE 1. Diffuse & Degrade Leaving the synapse

SYNAPSE

1. Diffuse & Degrade

Reuptake 2. Metabolism COMT or MAO SYNAPSE 1. Diffuse & Degrade Leaving the synapse free from
Reuptake 2. Metabolism COMT or MAO SYNAPSE 1. Diffuse & Degrade Leaving the synapse free from

Leaving the synapse free from stimulation

POSTSYNAPSE

The Monoamines

The Monoamines

THE MONOAMINES

↑Energy = Adrenalin Rush!!!
↑Energy = Adrenalin
Rush!!!

Metabolized by MAO enzymes

NOREPINEPHRINE (NE)

Excitatory transmitter of the brain and smooth muscles

↑Dopamine = ↑Desire 50% in the GIT
↑Dopamine = ↑Desire
50% in the GIT

DOPAMINE (Dopa)

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

Receptors are D 1 and D 2 (brain)

SEROTONIN (SE, 5-HT)

Released from inhibitory neurons

Stimulates either 5-HT 1 or 5-HT 2 receptors

Biosynhesis & Metabolism of Dopamine

Biosynthesis

Tyrosine

Tyrosine hydroxylase

DOPA

ALAAD

Dopamine

MAO

Dopamine

Metabolism

COMT 3-methoxytyramine
COMT
3-methoxytyramine

Dihydroxyphenylacetic acid

DOPA ALAAD Dopamine M A O Dopamine Metabolism COMT 3-methoxytyramine Dihydroxyphenylacetic acid Homovanillic acid
DOPA ALAAD Dopamine M A O Dopamine Metabolism COMT 3-methoxytyramine Dihydroxyphenylacetic acid Homovanillic acid

Homovanillic acid

Biosynthesis & Metabolism of NE

Biosynthesis

Tyrosine hydroxylase

ALAAD

Tyrosine

DOPA

NE

Metabolism

Tyrosine hydroxylase ALAAD Tyrosine DOPA NE Metabolism MAO Dihydroxymandelic acid MAO Dopamine Normetanephrine NE
Tyrosine hydroxylase ALAAD Tyrosine DOPA NE Metabolism MAO Dihydroxymandelic acid MAO Dopamine Normetanephrine NE

MAO

Dihydroxymandelic

acid

MAO

Dopamine

Normetanephrine

MAO Dihydroxymandelic acid MAO Dopamine Normetanephrine NE Dopamine β -hydroxylase (Sympathetic nerve) MAO

NE

Dopamine β-hydroxylase

(Sympathetic nerve)

MAO

Phenethanolamine-N-

methyltransferase

3-methoxy-4-hydroxy-mandelic acid

(Adrenal medulla)

EPI

Neurotransmitters

GABA Gamma Amino Butyric Acid

Inhibitory neurotransmitter of the brain

Binds to either GABA A or GABA B

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

Sympathetic

Autonomic Nervous System

preganglionic
preganglionic
preganglionic
preganglionic

preganglionic

preganglionic
postganglionic

postganglionic

postganglionic

Parasympathetic

Nervous System Sympathetic Autonomic Nervous System 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

Bronchodilation ↓GIT Activity ↑ Muscle Tone Bladder Relaxation = ↓ Urination Piloerection “Fight or Flight”

“Fight or Flight”

Bronchodilation ↓GIT Activity ↑ Muscle Tone Bladder Relaxation = ↓ Urination Piloerection “Fight or Flight”
Bronchodilation ↓GIT Activity ↑ Muscle Tone Bladder Relaxation = ↓ Urination Piloerection “Fight or Flight”
Bronchodilation ↓GIT Activity ↑ Muscle Tone Bladder Relaxation = ↓ Urination Piloerection “Fight or Flight”
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

“ R e s t & D i g e s t ” Constriction of

Rest & Digest

Constriction of Pupils

(Myosis)

↑ Salivation

↓ Heart beat (-) Inotropic & Chronotropic

Bronchoconstriction

↑ GIT Activity

Bladder Contraction = ↑ Urination

Essential for Life

Anabolic

Unfunctional entity

Discrete Never discharge as complete system

Cholinergic Nervous System “Rest and Digest”

cranial CRANIOSACRAL cervical thoracic lumbar
cranial
CRANIOSACRAL
cervical
thoracic
lumbar

sacral

THORACOLUMBAR
THORACOLUMBAR

CHOLINERGIC RECEPTORS

ACETYLCHOLINE RECEPTORS

NICOTINIC and MUSCARINIC

Nicotinic

subtypes are:

N N (neuronal)

N M (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 (IP 3 and DAG as second messengers)

Inhibition of adenylate cyclase

Activation of K + -channels or inhibition of Ca +2 - channels

Mediate Ach effects at postganglionic parasympathetic synapses (mainly heart,

smooth muscle, glands), and contribute to

ganglionic excitation.

M1 M3 M3 VASODILATION ↓PR = ↓BP M3
M1
M3
M3
VASODILATION
↓PR = ↓BP
M3

MIOSIS CILLIARY MUSCLE contraction ACCOMODATION

M3 M3
M3
M3

SLOW excitation of

ganglia :

DEPOLARIZATION

↑GLAND SECRETION = ↑Lacrimation,

Salivation &

Sweating

M2 M3 ↑release of NO = ↑BLADDER CONTRACTION = Voiding
M2
M3
↑release of NO =
↑BLADDER
CONTRACTION
= Voiding

BRONCHOSPASM ↑Secretion of mucus Bronchoconstriction (Slow deep breaths)

↓ HR & CONDUCTION VELOCITY (-) Chronotrpoic (SA node) (-) Dromotropic (AV node)

INHIBITORY!!! (Gi - G PROTEIN)

↑PERISTALSIS ↑GI Secretions

MUSCARINIC

RECEPTORS

NICOTINIC

RECEPTORS

N N N M
N N
N M

FAST excitation of

ganglia :

DEPOLARIZATION

N = Neuronal

N M FAST excitation of ganglia : DEPOLARIZATION N = Neuronal MUSCLE CONTRACTION Found In Skeletal

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 IP 3 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

The Alpha Receptors
The Alpha Receptors
α1
α1
α1
α1

MYDRIASIS RADIAL MUSCLE contraction

PILOERECTION

Goosebumps

– RADIAL MUSCLE contraction PILOERECTION Goosebumps α1 α2 α1 GLYCOGENOLYSIS & GLUCONEOGENESIS ↑SUGAR
α1 α2
α1
α2
α1
α1

GLYCOGENOLYSIS & GLUCONEOGENESIS ↑SUGAR = ↑ENERGY

CONSTRICTION of ARTERIES = ↑PR = ↑BP

= ↑ENERGY CONSTRICTION of ARTERIES = ↑PR = ↑BP α2 ↓ PR = ↓ BP DILATION
= ↑ENERGY CONSTRICTION of ARTERIES = ↑PR = ↑BP α2 ↓ PR = ↓ BP DILATION
α2
α2

PR = BP

DILATION of ARTERIES =

INHIBIT INSULIN RELEASE ↓ INSULIN = ↑SUGAR

= ↓ BP DILATION of ARTERIES = INHIBIT INSULIN RELEASE ↓ INSULIN = ↑SUGAR α2 INHIBITS
= ↓ BP DILATION of ARTERIES = INHIBIT INSULIN RELEASE ↓ INSULIN = ↑SUGAR α2 INHIBITS
α2
α2

INHIBITS NE RELEASE ↓NE = ↓BP

Effects of alpha 1 receptor activation

on different tissues and systems

Effects of alpha 1 receptor activation on different tissues and systems

Postsynaptic Alpha 1 Receptors on Vascular Smooth Muscle

Postsynaptic Alpha 1 Receptors on Vascular Smooth Muscle

Presynaptic Alpha 2 Receptors

Alpha 2 receptors also exist presynaptically associated with nerve terminals

Activation of these receptors inhibits the release of NE

NE acts at presynaptic alpha 2 receptors to inhibit its own release.

these receptors inhibits the release of NE – NE acts at presynaptic alpha 2 receptors to

Alpha-2 receptor activation

Alpha-2 receptor activation

Drugs affecting alpha receptors

Drugs affecting alpha receptors

LIPOLYSIS

LIPOLYSIS BRONCHODILATION Bronchioles relax (fast shallow breaths) β 2 β3 ↑GLUCONEOGENESIS & GLYCOGENOLYSIS

BRONCHODILATION Bronchioles relax (fast shallow breaths)

β2

β3

↑GLUCONEOGENESIS &

GLYCOGENOLYSIS

↑Sugar levels = ↑ENERGY

β1

↑ RENIN PRODUCTION = ↑PR = ↑BP (Juxtaglomerular Cells)

RENIN PRODUCTION = ↑PR = ↑BP (Juxtaglomerular Cells) β2 β1 β2 β2 ↑UPTAKE OF K in
β2 β1 β2 β2
β2
β1
β2
β2
= ↑PR = ↑BP (Juxtaglomerular Cells) β2 β1 β2 β2 ↑UPTAKE OF K in Muscles ↓K

↑UPTAKE OF K in Muscles ↓K levels in blood = HYPOKALEMIA

β2

(+) Chronotropy & (+) Inotropy ↑HR & ↑Force of Pumping

& (+) Inotropy ↑HR & ↑Force of Pumping URINARY RETENTION ↓GI MOTILITY Bladder relaxation (GU)

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

UTERINE RELAXATION

↑Force of Pumping URINARY RETENTION ↓GI MOTILITY Bladder relaxation (GU) Constipation (GIT) UTERINE RELAXATION

Effect of Beta 1 Receptor Activation on the Heart

Effect of Beta 1 Receptor Activation on the Heart

Effect of Beta 2 Receptor Activation on Smooth Muscle

Effect of Beta 2 Receptor Activation on Smooth Muscle • Leads to vascular and nonvascular smooth

Leads to vascular and

nonvascular smooth muscle

relaxation

Drugs that activate the beta 2 receptor can be;

used to treat as asthma

(by relaxing airway smooth muscle) and

premature labor (by relaxing

uterine smooth muscle).

USES OF SELECTIVE BETA 2 AGONISTS

1. Airways dysfunction; bronchial asthma,

chronic bronchitis, emphysema

In airways dysfunction, beta 2 selective agonists relax airways thus decreasing airways resistance

2. Premature labor

In premature labor, the beta 2 selective agonists relax uterine smooth muscle.

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

The Beta receptors

The Beta receptors
The Beta receptors

Main effects of ADRENERGIC receptor

Activation

Type of Receptor

Locations

Effects

α 1

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

α 2

Presynaptic nerve terminals

Inhibits release of NE (presynaptic inhibition)

Platelets Pancreatic β cells

Aggregation Inhibits insulin release (hyperglycemia)

Main effects of ADRENERGIC receptor

Activation

Type of Receptor

Locations

Effects

β 1

Heart

Incr in heart rate, contractility and conduction

Juxtaglomerular cells

Incr in secretion of renin (incr

BP)

β 2

Vascular smooth muscle Bronchiolar smooth muscle GI and urinary bladder smooth muscle

Vasodilation (relaxation) Bronchodilation (relaxation) Decr GI and GU motility (relaxation) Decr uterine contraction (relaxation) Uptake of K + in skeletal muscles Glycogenolysis & gluconeogenesis

Uterine smooth muscle

Skeletal muscle Liver

β 3

Adipose tissue

Lipolysis