CNS Stimulant drugs Pharmacology

1. CNS
STIMULANT
Prepared by-Shagufta Farooqui
Department of Pharmacology
Nanded Pharmacy College, Nanded

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These are drugs whose primary action is to stimulate the CNS
globally or to improve specific brain functions.
CNS stimulants are the psychoactive drugs that induce
temporary improvement in either mental or physical function
or both.
The CNS stimulants mostly produce a generalized action
which may, at high doses, result in convulsions.
Introduction

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 These are the drugs which increase the muscular (motor)
and the mental (sensory) activities.
 Their effects vary from the increase in the alertness and
wakefulness (as with caffeine).
 To the production of convulsion ( as with strychnine) or
death due to over stimulation.
CNS STIMULANT

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Types
Psychomotor
stimulants
Hallucinogens
or
Psychomimetic
drugs
Analeptics

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1. Analeptics
– Respiratory stimulants & Convulsants.
2. Psychomotor Stimulant
– Excitement & Euphoria
– Decrease feeling of Fatigue
– Increase Motor activity
3. Psychotomimetic Drugs ( Hallucinogens )
– Changes in Thought Patterns & Mood
– Little Effect on Brain stem & Spinal Cord

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A. Block neurotransmitters reuptake (Most reuptake
B. inhibitors affect either NE or 5- HT(Serotonin) : Cocaine
C. Promote neurotransmitters release : Amphetamine
D. Block Metabolism - MAO inhibitors (monoamine
oxidase):ex. Phenelzine
E. antagonize the effect of inhibitory neurotransmitter:
Picrotoxin & Strychnine
MOA of CNS stimulant

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Classification
Convulsants
Strychnine
Picrotoxin,
Bicuculline,
Pentylenetetra
zol,(PTZ).
Analeptics
Doxapram
Psychostimulant
s
Amphetamines,
Atomoxetine,
Modafinil,Cocaine,
Caffeine

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STRYCHNINE
It is an alkaloid from the seeds of Strychnos nux-
vomica, and a potent convulsant.
The convulsions are reflex, tonic-clonic and symmetrical.
It has been labelled as a spinal convulsant because the dose
producing convulsions is the same in spinal animals as in
intact animals; actually it stimulates the whole cerebrospinal
axis.

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STRYCHNINE
Strychnine was previously used as
1.Purgative
2.Appetite suppressant
3.Aphrodisiac
4.Constituent of nerve tonics.
Today, this potent alkaloid is mainly used as a rodenticide,
and for killing stray dogs (Nux vomica seeds are therefore
sometimes referred as “dog buttons”)

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Mechanism of Action
Strychnine is a neurotoxin act as a antagonist of
glycine,which is a inhibitory neurotransmitter.
Strychnine competitively and reversibly inhibit
neurotransmitter glycine at postsynaptic neuronal
sites in the spinal cord.

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Strychnine (spinal cord Stimulant)
A. Plant Alkaloid ( Indian Plant )
B. Poison …. Vermin, Stray dogs,
C. Tonic …. Very low dose ( both weary brain & debillitated persons )
D. Powerful convulsant
E. Opisthotonous Position
F. Violant Extensor spasm, Trigger With minor sensory stimuli
G. MIMMIC Symptoms of TETANUS TOXIN
H. Competitively Block receptors for GLYCINE
I. TETANUS toxin Block Release of GLYCINE from inhibitory neurons

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 Stiffness of muscles occurs before typical strychnine
convulsions occur.
 These convulsion are at first clonic (intermittent) and then
tonic (sustained) in nature.
 They affect simultaneously both the flexors and extensors.
•Opisthotonos:
 The muscle become stiff and rigid so that there is
hyperextension of the spine and body arched forward,
resting only on the back of head and heels.
 Sometimes the body curve is in the opposite direction
(Emprosthotonos or sideways Pleurosthotonos)

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Picrotoxin
Obtained from ‘fish berries’ of East Indies Anamirta cocculus. It is a potent
convulsant— convulsions are clonic, spontaneous and asymmetrical.
The convulsions are accompanied by vomiting, respiratory and vasomotor
stimulation. Though regarded as a medullary stimulant, it has little selectivity in
site of action.
Picrotoxin acts by blocking presynaptic inhibition mediated through GABA.
However, it is not a competitive antagonist; does not act on GABA receptor itself,
but on a distinct site and prevents Cl¯ channel opening. Diazepam, which
facilitates GABAergic transmission, is the drug of choice for
picrotoxin poisoning. Picrotoxin has no therapeutic indication now.

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Bicuculline
This synthetic convulsant has picrotoxin like actions.
It is a competitive GABAA receptor (intrinsic Cl¯ channel
receptor) antagonist, while GABAB receptor (G-protein
coupled receptor) is insensitive to it.
It is only a research tool.

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Pentylenetetrazol (PTZ, Metrazol, Leptazol)
It is a powerful CNS stimulant, believed to be acting by direct
depolarization of central neurones.
However, it has also been shown to interfere with GABAergic
inhibition—may be acting in a manner analogous to picrotoxin.
Low doses cause excitation, larger doses produce convulsions which
are similar in pattern to those caused by picrotoxin.
Antagonism of PTZ induced convulsions is an established method of
testing anticonvulsant drugs in laboratory animals
It is specifically a GABA-a receptor antagonist it acts at the
picrotoxin (PTX) site of the gamma-aminobutyric acid
type A (GABA(A)) receptor.

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ANALEPTICS (Respiratory stimulants)
These are drugs which stimulate respiration and can have resuscitative
value in coma or fainting.
They do stimulate respiration in subconvulsive doses, but the patient may get
convulsions while still in coma.
Mechanical support to respiration and other measures to improve circulation are
more effective and safe.
The role of analeptics in therapeutics is very limited.
Situations in which they may be employed are:
 As an expedient measure in hypnotic drug poisoning until mechanical
ventilation is instituted.
 Suffocation on drowning, acute respiratory insufficiency.
 Apnoea in premature infant.
 Failure to ventilate spontaneously after general anesthesia.
 However, the overall utility of analeptics is dubious.

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Doxapram
It acts by promoting excitation of central neurones.
At low doses it is more selective for the respiratory centre than other
analeptics. Respiration is stimulated through carotid and aortic body
chemoreceptors as well.
Falling BP rises. Continuous i.v. infusion of doxapram may abolish
episodes of apnoea in premature infant not responding to theophylline.

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Mechanism of action
Doxapram stimulates chemoreceptors
in the carotid bodies of the carotid arteries,
which in turn, stimulates the respiratory centre in the brain stem.

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Uses
A. Doxapramstimulate the respiratory rate in patients with
respiratory failure.
B. It may be useful for treating respiratory depression in
patients who have taken excessive doses of drugs such
as buprenorphin,
C. also used for recovery after anesthesia

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Psychomotor Stimulants
Marked effect on mental functions & Behavior
Produce Excitement, Euphoria
Reduce Sensation of Fatigue
Increase motor Activity

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Amphetamines
These are central sympathomimetics. Compared to amphetamine,
higher central: peripheral activity ratio is exhibited by
dextroamphetamine and methamphetamine.
They stimulate mental rather than motor activity; convulsive doses are
much higher. It is a potent CNS stimulants that is used in treatment of
ADHD, narcolepsy and obesity DEXTROAMPHETAMINE is major
member of this compound.
It is non catecholamine

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ADVERSE EFFECT
 Insomnia
 Irritability
 Weakness
 Dizziness
 Tremor
 Confusion
 Suicidal tendencies

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ATOMOXETINE
It is a nor epinephrine reuptake inhibitor approved for the
treatment of ADHD
• It is a NE reuptake inhibitor

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METHYLPHENIDATE
 It is a CNS stimulants of phenethylamine and piperidine classes that
is used in treatment of ADHD and narcolepsy
 Less potential for abuse than cocaine
 Properties similar to amphetamine and may also lead to abuse

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Modafinil
This newer psychostimulant is popular with night-shift (call centre)
workers and other professionals who want to improve alertness and keep
awake.
It is claimed to increase attention span and improve accuracy that has
been compromized by fatigue and sleepiness. Although, modafinil has been
shown to inhibit NA and DA uptake as well as alter junctional
concentration of glutamate and GABA, its actual mechanism of
action is not known.
The approved indications are day-time sleepiness due to narcolepsy,
sleepapnoea syndrome and shift-work disorder (SWD).
It has also been found to reduce euphoria produced by cocaine and to
suppress cocaine withdrawal symptoms; is being evaluated as a drug to
prevent relapse of cocaine dependence.

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Cocaine
Caffeine Out of the three naturally occurring methylxanthines, only
caffeine is used as a CNS stimulant.
Cocaine increase, mental alertness & produce a feeling of wellbeing &
euphoria that is similar to that caused by amphetamine like amphetamine
cocaine can produce hallucinations, delusion & paranoia cocaine increases
motor activity & at high doses causes tremors, convulsion & followed by
respiratory & vesomotor depression.
Uses
Cocaine has a local anesthetic action for the therapeutic use of cocaine,
cocaine is applied topically as a local anesthetic for eye, ear & nose & throat
surgery

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Adverse effects
Toxic effects of caffeine are extensions of its pharmacological
actions.
Caffeine poisoning is rare, and it is less toxic than
theophylline.
Gastric irritation, nausea and vomiting may occur as side
effects.
Excitatory and motor effects such as nervousness, insomnia,
agitation, muscular twitching, rigidity, rise in body
temperature, delirium and convulsions are produced at toxic
doses.

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Uses
1) In analgesic mixture: caffeine benefits headache probably
by allaying fatigue and boredom. It has no analgesic action
of its own.
2) Migraine: Caffeine is used in combination with ergotamine
for treatment of migraine attack. It appears to benefit by
augmenting constriction of cranial vessels and by enhancing
absorption of ergotamine from the g.i.t.
3) Apnoea in premature infants: as alternative to theophylline

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HALLUCINOGENS
A. Also called psychotomimetic
B. It is the stimulants that produce profound changes in
thought patterns & moods, with little effect on brain stem
& spinal cord
C. Incapable of normal decision making because drug
interfere with rational thought.

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Lysergic acid diethylamide
A. It is a psychedelic drug of ergoline family well known for its
psychological effects which can include altered thinking
processes, synesthesia, an altered sense of time & spiritual
experiences.
B. It is non addictive
USES
I. Treatment of alcoholism
II. Pain & cluster headache relief
III. End-of-life anxiety for
IV. Spiritual purpose & to enhance creativity

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Tetrahydrocannabinol (THC)
A. The main psychoactive alkaloid contained in marijuana is
THC which is available as DRONABINOL
B. THC can produce euphoria followed by drowsiness &
relaxation

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