Nervous system disorders

Lecture 3: Dr. Dina El-Kersh

 Nervous
system

PNS
CNS Nerves outside the brain or
spinal cord which connect CNS
Brain & spinal cord to limbs (Uppler & Lower)

Autonomic
Somatic
Involuntary activity
Voluntary activity Body requirements without
“Ms. Contractions” conscious participation of the
mind

Parasympathetic
Sympathetic
Return to normal after
Emergencies sympathetic stimulation
“Fight or flight”
Building unit of CNS & PNS: Neuron

Connection between two neurons

occurs through synapse.

Neuronal signals are transmitted

via the release of chemical
messengers (neurotransmitters)
by the presynaptic neuron.
 Neurotransmitters
• Glutamate: Major excitatory neurotransmitter in the CNS
• Dopamine (DA): Excitatory neurotransmitter that activates
“pleasure centers” & makes a person “feel good” as well as
involved in muscle control and function.
• Epinephrine (adrenaline) & norepinephrine (noradrenaline):
Excitatory neurotransmitters & hormones at the same time.
• Acetylcholine: Excitatory neurotransmitter in the CNS that plays
a critical synaptic role in the initial formation of memory. Also
Activates muscles in the PNS (e.g. skeletal muscle contraction).
• - aminobutyric acid (GABA): Major inhibitory neurotransmitter
in the brain.
• Adenosine: Inhibitory neurotransmitter, believed to play a role in
promoting sleep and suppressing arousal.
• Glycine: Major inhibitory neurotransmitter in the spinal cord
• 5-Hydroxytryptamine (Serotonin, 5-HT): Inhibitory
neurotransmitter whose imbalance is one of the most common
contributors to mood problems
 Sedatives & hypnotics
(Kava & Valerian)
Herbal drugs
CNS stimulants acting on the
(Tea, Coffee, Kola nut &
Cocoa seeds)
nervous
system
Antidepressants
(St. John’s wort)

Analgesics
(Opium, Willow & Capsicum)

Drugs used for (migraine Feverfew) &

toothache (Clove)

Drugs used for cognitive disorders & dementia (Alzheimer’s disease)

(Ginkgo)
 I. Sedatives & hypnotics
A sedative is a substance that induces sedation
by reducing irritability or excitement while a
hypnotic is a substance that induces sleep. They
are CNS depressants used for treatment of
anxiety, insomnia, agitation, convulsions.

The difference between sedative & hypnotic is generally

dose-dependent. Most synthetic sedatives & hypnotics
(e.g. benzodiazepines) have the problems of overdose,
habituation & addiction (c.f. herbal drugs)
Valeriana officinalis, Valerianaceae family.
• Active ingredients of valerian are valepotriates and
sesquiterpene volatile oils as valerenic acid.
• Sedation from valerian extracts results from
increase of GABA levels in the brain by inhibition
its catabolism & being a GABA receptor agonist.

Pregnant women should not use valerian because of its

potential to induce uterine contractions. Chronic
administration of valerian has been linked to
hepatotoxicity. Valerian can potentiate the effects of
other CNS depressants such as alcohol, opiates, barbitu-
rates, and BZDPs; they should not be taken concomitantly.
II. CNS stimulants

Therapeutically used CNS stimulants herbal drugs usually

contain caffeine whose mechanisms of action:
• Antagonism of adenosine receptors (adenosine
possesses an inhibitory effect on neuronal activity,
induce sleeping & suppress arousal).
• Release of adrenaline into the body so the body
remains active and alert.
• Increase dopamine production in the brain, so the
person experiences a temporary "high“, feels good and
stimulate pleasure centres.
 Caffeine

Examples of herbs containing caffeine as tea leaves,

Coffee bean, Kola nuts and Cacao seeds
Depression

It is postulated that deficiency of certain monoamine (MA)

neurotransmitters (serotonin, nor-epinephrine & dopamine) is
responsible for the corresponding features of depression.
Monoamine oxidase inhibition (MAO-I) preventing monoamine
degradation resulting in greater stores of monoamines available
for release.

M.O.A
Serotonin reuptake inhibition (restores serotonin levels in
synapses by preventing its reuptake by the presynaptic neurons
after impulse & subsequent degradation).
 IV. Analgesics
Drugs used to relieve pain
(painkillers) acting on both the
peripheral and central nervous
systems…

http://www.ncbi.nlm.nih.gov/pubmed/24055573
 Ginger pungent
ingredients
inhibit COX-II
enzymes “inhibit
formation of
proinflammatory
cytokines, so
anti-
inflammatory
effect.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018740/
 Ginger pungent
ingredients
inhibit COX-I
enzymes “GIT
protective PG
which synthesis
mucous lining

http://www.sciencedirect.com/science/article/pii/S0049384803004912
 Examples of analgesic herbal drugs
Drug Nature Plant name Main active Mechanism of action Photo
constituent(
s)
Opium Dried Papaver Morphine & Bind to opioid receptors
latex from somniferum codeine (involved in analgesia) in
fruits (Papaveraceae) alkaloids the CNS

Willow Bark Salix purpurea Salicin Salicin is converted by

& S. alba intestinal bacteria to sugar
(Salicaceae) & salicyl alcohol which is
oxidized in the blood,
tissues & liver to salicylic
acid (aspirin metabolite)
Capsicum Fruits Capsicum Capsaicin* Depletion of substance P
(Chili minimum pungent (a neuropeptide that
pepper) (Solanaceae) principle mediates the transmission
of pain impulses from the
peripheral nerves to the
spinal cord)+ counter
irritant effect.
• Morphine is a very potent analgesic for severe pain
(e.g. kidney stone) and post-operative surgery.
• Used for limited doses under medical supervision to
control side effects (e.g. respiratory depression,
constipation) & prevent addiction.

Morphine
 V. Drugs used for migraine & toothache

A. Migraine

A migraine can cause severe throbbing

pain or a pulsing sensation, unilateral,
affecting males: females 1:3. It's often
accompanied by nausea, vomiting, and
extreme sensitivity to light.
Etiology:
Triggers lead to neurovascular disorder due to
vasodilatation of cranial blood vessels by peptide
vasodilators which stimulate trigeminal sensory
nervous pain pathway leading to headache & pain,
followed by vasoconstriction of cranial vessels besides
release of proinflammatory mediators which causes
pain & headache.
• Depletion of serotonin on their receptors of the
trigeminal nerve “which help regulate pain in the
nervous system” resulting is migraine pain.
Aura
Disturbance occur before or during migraine attack.
They are usually visual disturbances, such as flashes
of light or wavy, zigzag vision.

Anxiety.
Stress.
Exposure to light.
Hormonal changes (females).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117050/
 Prophylactic herbal drug of
migraine attacks

Feverfew leaves

(Tanacetum parthenium, Asteraceae) The

main ingredients are sesquiterpene
lactones (Parthenolides)

Feverfew appears to be an inhibitor of proinflammatory cytokines,

relieve vasoconstriction of cranial blood vessels & muscles spasms.
 B. Tooth ache
Pain around the teeth or jaws
Etiology:
Dental cavities (caries)
Dental abscess (tooth infection due to pulp tissue death)
Cracked tooth
Exposed tooth root
Gum disease
Examples of herbal drugs used locally for treatment of tooth ache
Drug Nature Plant name Main active Mechanism of action
constituent(s)

Clove Flower buds Eugenia caryophyllata Volatile oil Analgesic & anti-
oil (Myrtaceae) 85 % eugenol inflammatory blocks
cyclooxygenase
pathway leading to
inhibition of PG
biosynthesis), local
anesthetic & antiseptic
(4As)
 VI. Drugs used for cognitive enhancement & dementia
(Alzheimer’s disease)

Alzheimer's disease (AD) is the most common form of

dementia among older people (usually begins after age 60).
Dementia is a brain disorder that seriously affects a person's
ability to carry out daily activities. AD is characterized by loss
of neurons and synapses in the cerebral cortex and certain
subcortical regions resulting in gross atrophy of & the
appearance of fibrous structures in the affected regions.
Symptoms: Developed gradually……

• Troubleshooting in remembering things that

happened recently or names of people they know.
• People may not recognize family members or have
trouble speaking, reading or writing & may forget
how to brush their teeth or comb their hair
• Later on, they may become anxious or aggressive, or
wander away from home

Etiology
The oldest hypothesis, on which most currently available drug
therapies are based, proposes that AD is caused by reduced
synthesis of the neurotransmitter acetylcholine.
Ginkgo leaves

Main active constituents: (GBE)

Diterpene lactones (ginkgolides & bilobalides) &
biflavone glycosides (e.g. ginkgetin)

Mechanism of action:

It slows the onset of dementia & delays the deterioration in

cognitive function in the early stages of AD:
❖ Improves cerebral circulation & blood flow into ischemic tissue.
❖ Free radical scavenging effect. (Anti-oxidant).
❖ Stimulation of the synthesis & inhibition of the synaptic
breakdown of Acetyl choline neurotransmitters & stimulates
the growth of receptor sites.
 Herbs containing alkaloids
“slow down the progression of AD for a period of time”
(Acetylcholinesterase inhibitors “anticholine esterase” AChE-I)

Alkaloid Rivastigmine Galantamine

Source Semi-synthetic derivative of bulbs & flowers
physostigmine found in (Galanthus nivalis,
Calabar beans (Physostigma Amarillydaceae)
venenosum, Fabaceae)
Structure
 Case Study
C.J, 75 years old, suffering from cognitive
disorders as inability to remember her husband
or kids names & recent situations happened to
her. This disorder last for several months which
cause her to be always aggressive, anxious and
irritable. Also she suffers from parkinson’s
disease since 2 year ago where she is talking
Levopoda treatment. The family physician
suggests her herbal medications according to
her case.