CNS STIMULANTS

(MOA and Uses)

Stimulants (Drugs of Abuse)
• “Stimulants are substances which tends to
increase behavioral activity when
administered”.

• “Drugs that speed up the CNS; produce

wakefulness and a sense of energy and well
being”.
• Stimulants are also referred as “uppers” as
they up your energy and alertness.

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 Central Nervous System Stimulation
It is the primary action of diverse group of
pharmacological agents and adverse effect associated
with many drugs.

Behavioral manifestation of CNS stimulation is ,

 Mild elevation in alertness, decrease in drowsiness
and lessening of fatigue (Analeptic Effect)
 Increased nervousness and anxiety
 Convulsions at high doses

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 General Signs & Symptoms

↑ Heart rate
↑ Respiratory rate
Instability
Tremors
Hair erection
Convulsion

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 Molecular Basis of CNS Stimulation
 Imbalance between the inhibitory and excitatory
processes as in brain. This hyperexcitability of
neurons results from:
 Potentiation or excitement of excitatory
neurotransmission (e.g Amphetamine)
 Depression or antagonism of inhibitory transmission
 (e.g Strychnine)
 Presynaptic control of neurotransmitter release (e.g
picrotoxin)

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 Classification of CNS Stimulants
A. - Psychomotor Stimulants
• Cause; excitement, euphoria, decreased feeling
of fatigue and locomotors activity, e.g
1. Amphetamine
2. Nicotine
3. Cocaine
4. Methylphenidate

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B. Hallucinogens (Pychotomimetics)

Affect; Thought, perception and mood, e.g

1. Lysergic acid diethylamide (LSD)
2. Tetrahydrocannabinol (THC)

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 Amphetamine
Is a non catecholamine (shows a neurologic
and clinical effects quite similar to those of
cocaine).
Dextroamphetamine is the major member of
this class of compounds,
Methamphetamine (Speed) is derivative of
amphetamine that can be smoked and it is
preferred by many abusers.

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 MOA:
Block the reuptake of
norepinephrine and
dopamine into the
presynaptic neuron and
increase the release of
these monoamines into
the extraneuronal
space.

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Actions
a) CNS:
Major behavioral effects of amphetamine results from
combination of the dopamine and NE release
properties
• Increased alertness
• Decreased fatigue
• Decreased appetite
• Insomina
b) Sympathetic Nervous system: By indirectly
stimulating the receptors through NE release

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 Clinical use:
1. Narcolepsy (Day time sleepiness):
 A rare sleep disorder characterized by uncontrollable bouts of
sleepiness during the day. It is sometimes accompanied by
catalepsy (loss of muscle control) and even paralysis brought
on by strong emotions such as laughter, however it is
sleepiness for which the patient is treated with drugs such as
Amphetamine or Methamphetamine.
 Recently Modafinil (wakefulness promoting agent) and its
R-enantiomer Amodafinil have become available to treat
narcolepsy. Modafinil produces few psychoactive and
euphoric effects with fewer alterations in perception, mood
,thinking and feelings typical of other CNS stimulants.

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Attention-deficit hyperactivity disorder (ADHD):
 Some young children are hyperkinetic and lack the ability to
be involved in any activity for longer than a few minutes.
Dextroamphetamine and the amphetamine derivative
methylphenidate can help improve attention spans and
alleviate many of the behavioral problems associated with this
syndrome, in addition to reducing the hyperkinesia that such
children demonstrate.

 Atomoxetine is a nonstimulant drug approved for ADHD in

children and adults. It is a norepinephrine-reuptake inhibitor.
Therefore, it is not habit forming and is not a controlled
substance.

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 Nicotine
It is active ingredient in tobacco
Nicotine remains important because:

 It is 2nd only to caffeine as most widely used

 It is 2nd only to alcohol as most abused drug

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 MOA

In low doses, nicotine causes ganglionic stimulation

by depolarization.
 At high doses, nicotine causes ganglionic blockade.
Nicotine receptors exist at a number of sites in the
CNS, which participate in the stimulant attributes of
the drug.

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 Uses
Used in smoking cessation

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 Cocaine (Highly Addictive Drug)
Strong stimulant mostly used as a recreational drug.
Commonly snorted , inhaled or injected into the
veins.
It is addictive and after short period of use, there is
high risk that dependence will occur.

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 MOA
Blockade of the reuptake of
the monoamine(NE, serotonin
and Dopamine) into the
presynaptic terminals from
which these neurotransmitters
are released.
Thus potentiate the CNS
and peripheral effects of
these neurotransmitters.

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 Actions
 Initially produces euphoria (similar to amphetamine)
by prolongation of dopaminergic effects in the brain’s
pleasure system (Limbic system)
 Chronic intake of cocaine depletes dopamine. This
depletion triggers vicious cycle of craving for cocaine
that relieves severe depression.

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 Sympathetic nervous system: Cocaine potentiate the
action of NE and it produces the” fight and flight”
syndrome characteristic of adrenergic stimulation
associated with,
• Tachycardia
• Hypertension
• Pupillary dilation
• Peripheral vasoconstriction
 Hyperthermia: Cocaine is unique among illicit drugs
that death can result not only as a fraction of dose but
but also from drug’s propensity from hyperthermia.

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 Uses
Its clinical use is as local anesthetic in
particular in eye, ear and throat surgery.
Cocaine is the only local anesthetic that causes
vasoconstriction

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 Methylphenidate
It has CNS stimulant properties similar to those of
amphetamine and may also lead to abuse.
Methylphenidate is more potent dopamine transport
inhibitor than cocaine thus making more dopamine
available.
It has less potential for abuse than cocaine , because it
enters the brain much more slowly than cocaine and
does not increase dopamine levels as rapidly.

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 Uses
1. ADHD :
Methylphenidate and its active isomer
,Dexmethylphenidate have been used for
decades in the treatment of ADHD in children
aged 6 to 16.
2. Narcolepsy:
It is also effective in treatment of narcolepsy.

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Hallucinogens
• Hallucinogens (also referred to as psychedelic or
Psychomimetic drugs and Psychotogens) .

• Hallucinogens are a class of drugs that cause hallucinations—

profound distortions in a person’s perceptions of reality
accompanied with bright colorful changes in environment and
by a plasticity of constantly changing shapes and colors.

• They produce profound changes in thought patterns and mood

with little effect on brain stem and spinal cord .

• Incable of normal decision making because drug interfere with

normal rational thought
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 Classification of Hallucinogens
Serotonergic Cholinergic
 LSD
 Muscarine
 Psilocybin/Psilocin
 Scopolamine
 DMT - Ayahuaca
Glutamatergic
 Bufotenine
Catecholamine-like  PCP
 Mescaline  Ketamine
 MDMA (ecstasy)  Dextromethorphan
MDA Opioid
MDE  Salvinorin A
 DOM
 Myristin

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 Lysergic Acid Diethylamide (LSD)
It is also known as acid, blotter, doses, hits, microdots, sugar
cubes, trips, tabs, or window panes—is one of the most potent
mood- and perception- altering hallucinogenic drugs.
It is an exceptionally potent psychotomimetic drug.
It is not considered an addictive drug since it does not produce
compulsive drug-seeking behavior.
Users refer to their experience as a “trip” and to acute adverse
reactions as a “bad trip”.
These experiences are long and typically begin to clear after
about 12 hours.

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 Actions of LSD
Massive increase in neural activity in some brain
regions
- Activates sympathetic nervous system (causes
pupillary dilation, increased blood pressure,
piloerection, and increased body temperature)
- Parasympathetic nervous system (increase in
salivation and nausea)

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 MOA
Multiple sites in the CNS are affected by lysergic
acid diethylamide (LSD.
The drug shows serotonin (5-HT) agonist activity at
presynaptic 5-HT1 receptors in the midbrain, and it
also stimulates 5-HT2 receptors.

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 Uses
Treatment of alcoholism
Pain and cluster headache relief
End of life anxiety for spiritual purpose and to
enhance creativity

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 Tetrahydrocannabinol (THC)
The main psychoactive alkaloid contained in
marijuana is THC which is available as
Dronabinol .
THC produce euphoria
followed by drowsiness
and relaxation.

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 MOA
THC receptors, designated as CB1 receptors have
been found on inhibitory presynaptic nerve terminals.
CB1 is coupled to G protein.
Interestingly endocannbinoids have been identified in
the CNS.
The compounds which bind to the CB1 receptors, are
membrane derived and are synthesized on demand,
they may act as local neuromodulators.
The action of THC is believed to be mediated through
CB1 receptors but is still under investigation.

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 Actions
THC has a variety of pharmacologic effects that resemble
those of amphetamines, LSD, alcohol, sedatives, atropine, and
morphine.

The early stage is one of being "high" and is characterized by

euphoria, uncontrollable laughter, alteration of time sense,
depersonalization, and sharpened vision.

Later, the user becomes relaxed and experiences introspective

and dream-like states if not actual sleep.

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 USES
1. Pain Relief
One of the most common uses of medical marijuana is for pain
relief. And as it turns out, THC is responsible for its pain-
relieving effects.
Likewise, cannabis has been shown to be especially effective
against neuropathic pain, or nerve-related pain.
2. PTSD
Post-traumatic stress disorder (PTSD) is another common
reason to use medical marijuana. The high from THC is also
associated with temporary impairments of memory.

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 Impaired memory is often therapeutic for those who struggle
to forget painful memories, such as patients who suffer from
PTSD. Recent studies confirm that oral doses of THC can help
relieve a variety of PTSD-related symptoms including
flashbacks, agitation and nightmares.
3. Nausea and Vomiting
THC has been available in pill form for treating nausea and
vomiting in cancer patients since the 1980s.
Marinol, a pill containing synthetic THC, was the first THC-
based medication to be approved by the FDA for this purpose.
Since then, other THC pills have been developed and
prescribed to patients undergoing chemotherapy, including a
pill called Cesamet.

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4. Appetite Stimulant
THC is known to work as a powerful appetite stimulant in both healthy and
sick individuals. Similarly, Marinol and Cesamet are regularly prescribed
to boost appetite in patients with cancer and HIV-associated wasting
syndrome.
A number of studies conducted with Marinol suggest that THC can also
stimulate weight gain in patients with anorexia.
5. Asthma
• Treating asthma may not seem like an obvious use for medical marijuana.
But as it turns out, THC’s ability to improve breathing in asthmatics is
supported by research dating back to the 1970s.
6. Galucoma
In 1971, during a systematic investigation of its effects in healthy cannabis
users, it was observed that cannabis reduces intraocular pressure.

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 Phencyclidine(PCP)
Phencyclidine (also known as PCP, or “angel dust”) was
originally intended as an intravenous anesthetic agent, but was
found to produce in many patients a period of disorientation
and hallucinations following recovery of consciousness.
Ketamine, a close analogue of phencyclidine, is better as an
anesthetic, although it too can cause symptoms of
disorientation.
Since the 1970s, PCP and more recently ketamine have
become widely accepted by drug abusers as desirable
hallucinogenic agents.
Phencyclidine may be smoked (by mixing the powder with
tobacco), "snorted," taken orally, or injected intravenously.

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 MOA
PCP inhibits the reuptake of dopamine, 5-HT, and
norepinephrine.
Receptors for PCP have been identified in the brain, and PCP
acts as an antagonist on the N-methyl-D-aspartate (NMDA)
subtype of glutamate receptors.
It is believed that the NMDA channel-blocking action is
primarily responsible for the psychotomimetic effects, which
mimic, both behaviorally and biochemically, the
manifestations of human schizophrenia.
Phencyclidine is known to exacerbate symptoms in stabilized
schizophrenic patients.

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 Uses
Phencyclidine has no therapeutic applications.

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 References
Essentials of Medical Pharmacology by K.D Tripathy7th
edition page no.374- 386
Lippincot’s Essentials of Pharmacology, 5th edition
http://www.leafscience.com/2014/07/22/7-proven-
medical-benefits-thc/

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