CNS stimulants increase mental and physical activity by blocking neurotransmitter reuptake or promoting release. They are classified based on their site of action in the brain or spinal cord and mechanism of action. While they have therapeutic uses for conditions like ADHD and narcolepsy, CNS stimulants can also cause adverse effects like euphoria, insomnia, convulsions, and addiction if misused.

1. CNS Stimulants
Definition
“Stimulant is a substance which
tends to increase behavioral
activity when administered”
CNS stimulants are drugs which
increase the muscular (motor) and
the mental (sensory) activities
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2. CNS Stimulants
 - They can be divided based on their site
of action:
 1.Cerebral stimulants (amphetamines)
 2.Medullary stimulants (picrotoxin)
 3.Spinal stimulants (strychnine)
 4. Psychomimetics (cannabinoids)
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3. Neurotransmitters CNS
 They can be classified into :
 1. Excitatory:
 - Ach, glutamate, aspartate ,
serotonin and NE.
 2. Inhibitory:-
 - GABA , glycin
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4. MOA of CNS Stimulants
1- Block neurotransmitters
reuptake (Most reuptake inhibitors affect
either NE or 5HT Cocaine
2- Promote neurotransmitters release :
Amphetamine
3- Block Metabolism - MAO inhibitors
(monoamine oxidase):ex. Phenelzine
4. antagonize the effect of inhibitory
neurotransmitter: Picrotoxin & Strychnine
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5. CNS Stimulants: Uses
Attention deficit hyperactivity disorder
drug-induced respiratory depression
 postanesthesia respiratory depression
narcolepsy
 sleep apnea
 exogenous obesity
 fatigue
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6. CNS Stimulants: Adverse
Reactions
 Neuromuscular reactions:
Excessive CNS stimulation;
headache
dizziness; apprehension;
disorientation hyperactivity
 Other:
 Nausea; vomiting; cough; dyspnea;
urinary retention; tachycardia;
palpitations; anorexia
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7. CNS Stimulants: Contraindications
CNS stimulants contraindicated:
In patients with known hypersensitivity
convulsive disorders;
 ventilation mechanism disorders :
Cardiac problems; severe hypertension;
 hyperthyroidism
Amphetamines:
*Contraindicated in glaucoma
*Amphetamines and anorexiants should not
be taken concurrently or within 14 days of
antidepressant medications
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8. Abuse potential
 Stimulants have been abused for both
“performance enhancement” and
recreational purposes (i.e., to get high).
 increase wakefulness,
 increase focus and attention...
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9. Classification of CNS
Stimulants
 Analeptic Stimulants
 Respiratory Stimulants
 Convulsants
 Psychomotor Stimulant
 Sympathomimetics or Adrenergic CNS
Stimulants
 Methylxanthines
 Psychomimetics

10. Analeptic Stimulants
 diverse chemical class of agents
 majority can be absorbed orally
 have a short duration of action - primary
expression of pharmacological effect is
convulsions (tonic-clonic) uncoordinated
 pharmacological effect is terminated through
hepatic metabolism
 Possible Common Mechanism of Action -ability to
alter movement of chloride ions across neuronal
membranes
 Therapeutic Uses Group as a whole has limited
therapeutic use.

11.  Doxapram and Nikithamide - used to
counteract postanesthetic respiratory depression
and for acute hypercapnia in chronic pulmonary
disease.
 Pentylenetetrazole - used clinically as a tool for
screening latent epileptics and experimentally to
screen compounds for anti-epileptic activity.
 Picrotoxin - used to study CNS mechanisms; it
interferes with pathways that are strychnine
resistant.

12. Spinal Cord Stimulants
Strychnine
MOA:
Blocking the action of glycine in spinal
cord
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13.  Strychnine is a source of accidental poisoning.
Also used to study CNS mechanism because of
its relatively specific action as a glycine
antagonist.
 Adverse Reactions:
Convulsion is characterized by opisthotonos, i.e.,
tonic extension of body and all limbs. Back is
arched and only the back of the head and the
heels are touching the touching the surface. All
sensory stimuli produce exaggerated response
and slight sensory stimulation may trigger
convulsion.

14. Spinal Cord Stimulants:
Cont.
Signs produced by spinal cord stimulants:
In large doses strychnine causes TONIC
CONVULSION
Characteristics of tonic convulsion:
1- Symmetric
2- Non-coordinated
3- Continuous
4- Reflex in origin
5- Characteristic arched back
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15. Treatment of Strychnine
Poisoning
(1) Remove/reduce external sensory stimuli
(2) Diazepam or Clonazepam I.V. or nitrous
oxide by inhalation to depress CNS and
stop convulsions which can be fatal

16. PSYCHOMOTOR STIMULANTS
 Drugs of Primary Importance
Amphetamine - prototype
Methamphetamine
Methylphenidate

17. Amphetamine
MOAs :
 Block the reuptake of norepinephrine and
dopamine into the presynaptic neuron and
increase the release of these monoamines
into the extraneuronal space
Clinical use:
1. Narcolepsy.
2. Attention-deficit hyperactivity disorder
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18. Mechanisms of Action
 Releases monoamines at synapses in
the brain and spinal cord.
 Inhibits neuronal uptake of monoamine
 Direct agonist of DA and 5-HT receptors
 Antagonist at certain adrenreceptors
 May inhibit monoamine oxidase.

19. CHARACTERISTICS
 all compounds are absorbed well orally
 large portion of untransformed amphetamine is
excreted unchanged
 in the urine. Consequently, acidifying the urine
with ammonium chloride hastens its clearance,
and thus reduces its reabsorption in the renal
tubules.
 Overdose: hyperreflexia, tremors and
convulsions
 Fatalities: hyperthermia rather than
cardiovascular effects

20. Pharmacological Actions
 The primary effects of an oral dose are
wakefulness, alertness, decrease fatigue;
mood elevation, increased ability to
concentrate; an increase in motor and
speech activity. Amphetamines also
diminish the awareness of fatigue;
person may push exertion to the point of
severe damage or even death.

21.  Stimulate the respiratory center, especially when
respiration is depressed by centrally acting drugs,
(barbiturates and alcohol).
 Amphetamine can reverse the marked sedation
and behavioral retardation resulting from
reserpine-like drug.
 Depresses appetite by their action on the lateral
hypothalamus rather than an effect on metabolic
rate.

22. Therapeutic Uses
 Hyperkinesias - Methylphenidate
 Narcolepsy - Amphetamine or
methylphenidate
 Obesity - Fenfluramine

23. Adverse Effects
 CNS: Euphoria, dizziness, tremor, irritability,
insomnia, Convulsion (at higher doses),
hyperthermia and coma
 C.V. Cardiac stimulation leads to headache,
palpitations, cardiac arrhythmias, anginal pain
 Other: Weight loss, Psychotic Reaction which
are often misdiagnosed as schizophrenia.
 Addiction - including psychic dependence,
tolerance and physical dependence.

24.  Drug Interactions:
 Tricyclic antidepressant
 Antihypertensive Agents
 Foods high in tyramine content

25. Methylphenidate
 Increasing dopamine levels in the brain
 dopamine is a neurotransmitter associated
with pleasure, movement, and attention.
 The therapeutic effect of stimulants is
achieved by slow and steady increases of
dopamine.
 Improves behavioural and learning ability
 Concentration span in adults
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26. Modafinil:
Exact mechanism of action is not known
but drug is thought to increase dopamine
conc.
Popular with night-shift workers- to be
awake improves attention span and
alertness
Allays fatigue and day time sleepiness
Sleep apnoea syndrome
Dose – 100 – 200 mg morning and
afternoon or 200mg 1 hr before starting
night-shift work
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27. METHYLXANTINES
 Caffeine:
 Coffee (100-150 mg/cup)
 Tea (30-40 mg/cups)
 Cocoa (15-18mg/cup)
 Theophylline: Tea and cocoa
 Theobromine: Cocoa

28. Mechanisms of Action
 Increase cyclic nucleotide concentration
 Blocks adenosine receptors
 Alters intracellular calcium distribution

29.  Caffeine, the most widely used drug in
the world, is a stimulant. Commonly
found in coffee, tea, soft drinks,
chocolate and a wide variety of over-the-
counter medications, it is legal to buy and
easily accessible.
 Caffeine is a physically addictive drug

30. Pharmacological Activity/
Adverse Effects
 Low Doses: 50-250mg/Caffeine (Oral Doses)
Increase mental alertness, decrease
drowsiness Lessen fatigue
 Larger Doses: 250-600mg/Caffeine Irritability,
restlessness, tremor, insomnia, headache,
palpitations and hyperesthesia GIT upset
 Large Doses: > 1000 mg Overt excitement,
delirium and clonic seizures

31.  Cardiovascular System: Increase rate
and force of the heart by directly
stimulating myocardium (low doses)
Tachycardia and arrhythmias at higher
doses. Peripheral vasodilation decease
in blood pressure (acute administration)
Hypotension and cardiac arrest (rapid i.v.
theophyline)

32.  Smooth Muscles: Relaxes vascular
smooth muscle (Theophylline »Caffeine)
 Kidney: All xanthines are capable of
producing some degree of diuresis in
humans (Theophylline > Caffeine)
 Miscellaneous: Xanthines shorten
clotting time by increasing tissue
prothrombin and factor V.

33. Adverse effects
 Stimulate gastric secretions in patients
with ulcer
 Dehydration in children due to vomiting
and transient diuretic action (theophyline)
 Allergic reaction (aminophylline)
 Psychic Dependence (Caffeine)

34. Therapeutic Uses
 Caffeine + plus ergot alkaloid
(Ergotamine): used to treat migraine
headaches
 OTC preparations: Theophylline:
Prophylaxis for chronic asthma
Respiratory Stimulant Bronchodilator for
relief of asthmatic symptoms

35. NICOTINE
 CNS Effects:
 Powerful CNS stimulant at lower doses;
Large doses produce clonic convulsion, then
depress CNS, compounding postictal
depression
 Stimulates respiration
 Produces emesis
 Tolerance to central actions with chronic use

36.  Cardiovascular Effects
 Tachycardia
 Increased blood pressure
 Pupillary constriction
 Cardiovascular collapse - due to CNS
depression
 Ganglionic blockade and arrhythmias
Fatalities: Due to respiratory failure

37. COCAINE
 Psychomotor stimulant
 local anesthetic
 Chemistry- alkaloid from coca plant
alkaloid is highly lipid-soluble
hydrochloride salt is water soluble

38. Routes of Administration
 Chewing: with an-alkaloid material (South
America)
 Sniffing: hydrochloride salt -absorption: nasal
mucous membranes -local vasoconstriction slows
absorption and prolongs effect
 Oral: large doses are needed for effect rapid onset
 Smoking: cocaine is converted to alkaloid
(freebase or "crack") which is readily volatilized
undegraded at lower temperature. I.V. and
smoking: reaches CNS in seconds in high
concentration produces more immediate and
intense effects

39. Pharmacokinetics
 large vol. of distribution
 quickly metabolized: half-life 30-90 minutes
 principal metabolites: a) Ecogonine
methylester - inactive b) Benzoylecogonine -
inactive c) norcocaine - active
 half lives of metabolites: 4 to 6 hrs. -
metabolites: Excreted in urine
 Drug Testing: BE - detectable for 1-3 days
Cocaine - detectable for a few hours

40. Psychotomimetics(
Psychedelics)
Their action mimic psychosis
1.Lysergic Acid Diethylamide(LSD)
2.Mescaline
3.Phencyclidine
4.Cannabinoids
Exceptins: Atropine,Antimalarials,Opioids(as
they causea alteration in sensory
perceptions in toxic doses only.

41.  These drugs substitute the present world by
alternate new world, so also called mind
expanders or fantasticants.
 They produce changes in sensory perceptions
 (visual,auditory,olfactory),thoughts, behaviour
 and mood(state of feeling at a time).
 Percepts:such thoughts or messages originating
from outside but have agreement with external
reality and signals.

42.  Fantasies:Messages synthesized inside
our head but do not have relationship
with reality.
 Dream:Fantasy occuring during sleep.
 Hallucination:Fantsy occuring during
wakeful state(false perception without a
true sensory stimulus. In it images are
vague and disproportionate.

43. Cannabinoids(Tetrahydrocan
nabinol)
 CB1 Rs in brain,CB2 Rs in periphery(L. system).
 THC is the active principle of hemp plant
(C.sativa ,C. indica) most popular drug of abus
 1.dried leaves powdered,make paste,drink.
 2. dried leaves powdered , smoked(marijuana)
 3.Resinous exudates of flower tops(charas).
 Actions:CNS stimulation followed by sedation.
 Euphoria,^ talkings,appetite,confidence,alert.
 ^ laughing or weeping(acc to company,music).

44.  Sedative phase:Time is passing slowly,fixed
statures(PINK). Memory,learning,motor fn dec
 Others: ^ HR,vaso and bronco dilatation,analg
 Antiemetic actions.
 Derivatives:1.Anadamide.
 2.Dronabinol: As appetizer in AIDS patients.
,antiemetic in cancer therapy e.g. Cisplatin
 3.Nabilone: As appetizer in AIDS patients.
 4.Rimonabent:To treat exogenous obesity.20 mg

45.  Thank you
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