This document discusses CNS stimulants and nootropic agents. It provides classifications and descriptions of various CNS stimulants including amphetamines, cocaine, caffeine, nicotine, and convulsants. It also discusses the mechanisms of action, uses, and adverse effects of nootropic agents that act as cholinergic activators like rivastigmine and donepezil, the glutamate antagonist memantine, and miscellaneous nootropics like piracetam and citicoline. The document aims to describe the pharmacology of these classes of drugs and their effects on cognition, memory, and brain function.

1. CNS STIMULANTS
&
NOOTROPIC AGENTS

2. Learning Objectives – CNS Stimulants & Nootropic Agents
At the end of the session, student should know
 Enumerate: CNS stimulants & Nootropic agents
 Describe the routes of administration, mechanism of action and adverse effects
(signs and symptoms of overdose, teratogenic effects, withdrawal effects) of the
following drugs:
 Amphetamine & related compounds
 CNS Stimulants: Strychnine; Pentylenetetrazol (PTZ); Doxapram; Caffeine,
Nicotine
 Briefly describe the mechanism of action, clinical uses and adverse effects of the
following nootropic agents:
 Anticholinesterases: Rivastigmine; Donepezil
 Memantine
 Piracetam
 Citicoline & Ginkgo biloba

3. CNS STIMULANTS

4. CNS Stimulants
 Drugs which elevate Mood, Increase feelings of well-being,
Increase energy & Alertness & Suppress appetite  CNS
Stimulants.

5. CNS Stimulants
 Drug which affect Thought, Perception & Mood 
Hallucinogens or Psychomimetics.
 Drug cause Excitement, Euphoria, Decrease feeling of
fatigue & Increase motor activity Psychomotor
Stimulants.

6. CONVULSANTS
RESPIRATORY
STIMULANTS
PSYCHO
-STIMULANTS
Classification
CNS Stimulants
DOXAPRAM
NIKETHAMIDE*
STRYCHNINE
PICROTOXIN
BICUCULLINE
PENTYLENETETRAZOL
AMPHETAMINES
METHYL PHENIDATE
ATOMOXETINE
MODAFINIL
ARMODAFINIL
PEMOLINE*
COCAINE
CAFFEINE
NICOTINE*

7. Convulsants  Strychnine
Alkaloid obtained from seeds of
Nux-vomica
Produces Reflex, Tonic Clonic &
Symmetrical Convulsions
Acts by blocking post synaptic
inhibition produced by the
inhibitory transmitter of glycine

8. Convulsants  Strychnine
Due to loss of synaptic inhibition any nerve
impulse become generalized causing Excitation &
Convulsions
No clinical use for strychnine
Poisoning  Diazepam or Clonazepam
Also 1:1000 KMNO4 or Tannic acid (2%)  To
absorb the alkaloid.

9. Pentylenetetrazol (PTZ) or Leptazol
CNS stimulant  Direct effect on Central neurons 

Produces convulsion
 Medullary stimulant  used as a Respiratory stimulant
Mainly used in experimental purpose
Poisoning treated with Diazepam
Low dose cause Excitation
Larger dose cause Convulsion

10. Picrotoxin
 Fish-berries of East Indies Anamirta
Cocculus.
 Potent Convulsant  Which is Clonic,
Spontaneous & Asymmetrical
 Blocking presynaptic inhibition mediated
through GABA
 Noncompetitive antagonist for GABAA
chloride channels  but it does not act
through the GABA receptor
 Diazepam which facilitates GABA
transmission is the drug of choice for
Picrotoxin poisoning.

11. Bicuculline
Synthetic Convulsant has Picrotoxin like action
Competitive GABAA receptor antagonist
Research purpose

12. Respiratory Stimulants (Analeptics)
 It Stimulate Respiration  in
Subconvulsive doses only
 Role of analeptics
As an useful measure in hypnotic
drug poisoning until mechanical
ventilation is instituted
Suffocation on drowning
Apnoea in premature infant
Failure to ventilate spontaneously
after general anesthesia

13. Doxapram
 Respiration is stimulated through stimulation of
central neurons
 Act mainly on Brainstem & Spinal Cord
 Increase activity of Medullary Respiratory &
Vasomotor center
 Low doses can selectively stimulate the
Respiration
 Dose 40-80 mg I.M. or 20mg /ml I.V.
 ROA I.V. infusion or I.M.

14. Psychomotor Stimulants -
Amphetamines
 Indirect sympathomimetics  Adrenergic neuron to
release NA
 Similar pharmacological profile to Ephedrine
 It potent CNS stimulant & weaker peripheral
Cardiovascular actions
 Both higher Central : Peripheral activity ratio exhibited
by Dextroamphetamines & Methamphetamine  usual
doses produce few peripheral effects
 They are stimulate Mental rather than Motor activity
 It orally active  Produce long duration of action 4-6 hr

15. Amphetamines
 Central action  by release of NA from adrenergic
neurons in brain
 By exchange diffusion & reverse transport involving
transporters like Norepinephrine transporter (NET),
Dopamine transporter (DAT) & Vesicular monoamine
transporter (VMAT2)
 Effects on Locomotor activity, Perception & Psychotic
Phenomena seen at higher doses Due to DA & 5-HT
release
 In addition, It inhibits neuronal reuptake of DA
 CNS effects  Alertness, Increased Concentration,
Attention Span, Euphoria, Talkativeness, Increased work
capacity
 Fatigue is allayed

16. Amphetamines
 Athletic performance is improved temporarily followed
by deterioration  “Dope test”
 Use before examinations to keep awake can counter
productive & needs to be condemned
 Respiratory stimulant  if it has been depressed
 Hunger is suppressed  inhibition of hypothalamic
feeding centre
 Week Anticonvulsant, Analgesic & Antiemetic actions :
Potentiate antiepileptic, Analgesics & Anti motion
sickness drugs

17. Methylxanthines
Caffeine, Theophylline & Theobromine:
Coffee  Caffeine
Tea  Theophylline & Caffeine
Cocca  Caffeine & Theobromine

18. Caffeine
Pharmacological action:
CNS  C & The – CNS stimulant
Caffeine  Stimulate the Respiratory Centre
CVS Increase force of contraction, Increase
HR & CO  Peripheral vasodilation  Decrease
in BP (not consistent) Vasoconstriction of
cerebral blood vessels.

19. Caffeine
Pharmacological action:
Kidneys  Diuretic effects
Smooth muscles  Relaxation (Bronchial SM)
Skeletal muscles  Enhance the power of
Muscle contraction
GIT Increase the secretion of Acid & Pepsin 

Gastric Irritants.

20. Caffeine
Pharmacokinetics:
Poor water solubility.
Completely metabolized in liver & finally excreted
in urine.
Half life 7-12 hr
Higher doses half life may be prolonged
Premature infants have a longer t1/2 24-36 hr

21. Caffeine
Adverse effects:
Gastric irritation
Nervousness, Insomnia, Agitation, Rise in
body temperature
Tachycardia, Hypotension, Nausea, Vomiting
Diuresis
High doses produce Convulsion
Tolerance develops after sometimes
Habituation to caffeine is very common

22. Caffeine
Uses:
In analgesic mixture (Aspirin / Paracetamol) 

benefits in Headache treatment
Combine with Ergotamine for relief of Migraine 

helps by constricting Cranial vessels
Branchial asthma  Theophylline
Apnoea in premature infants

23. ROA of CNS Stimulants
Amphetamine Injected, Swallowed, Smoked…
Cocaine hydrochloride Injected, Smoked,
Snorted….
Methamphetamine Injected, Swallowed, Smoked,
Snorted
Methylphenidate  Injected, Swallowed, Snorted
Nicotine  Cigarettes, Cigars, Smokeless Tobacco,
Bidis, Snorted, Taken in snuff

24. ROA of CNS Stimulants

25. Cocaine
Natural alkaloids from leaves Erythroxylon coca
Prominent CNS stimulation on Mood & Behaviour
Little Physical dependence drug
It blocks uptake of NA & Adr into adrenergic nerve
ending  higher concentration of NT  potentiate
of directly acting Sympathomimetic & suppression of
indirectly acting Sympathomimetic.

26. Symptoms of Cocaine use
Exaggerated feeling of well-being (Euphoria)
Dilated pupils
Increase heart rate
Restlessness & Hyperactivity
Symptoms of Cocaine withdrawal
Fatigue & Malaise
 Depression
 Very clear & Unpleasant dreams

27. Methylphenidate
Chemically similar to Amphetamine
Well absorbed orally & given as twice daily
dosage
Acts by releasing NA & DA in brain
It is superior to Amphetamines for treatment of
Hyperkinetic children (ADHD)

28. Modafanil
Popular with night shift (call centre) workers &
others who want to improve alertness & keep
awake
Increases attention span
Used for - day time sleepiness due to narcolepsy
& shift work sleep disorder
Most common side effect  Insomnia & Headache
Dose  100-200 mg morning & afternoon for day
time sleepiness due to narcolepsy.

29. NOOTROPIC AGENTS

30. Cognition Enhancers
 Developed for use in Dementia & Alzheimer's
disease
The mechanism by which they are believed to act are
 Increased Global / Regional blood flow
 Direct support of Neuronal metabolism
 Enhancement of Neuro transmission
 Improvement of Memory

31. CHOLINERGIC
ACTIVATORS
GLUTAMATE
ANTAGONIST
MISCELLANEOUS
TACRINE
RIVASTIGMINE
DONEPEZIL
GALANTAMINE
MEMANTINE PIRACETAM
PYRITINOL
DIHYDROERGOTOXINE
CITICOLINE
PIRIBEDIL
GINKGO BILOBA
Classification
Nootropic Agents

32. Cholinergic Activators
Since, brain Ach levels are markedly & cholinergic
transmission is also affected in AD, various
approaches to brain Ach have been tried.
Tacrine  Centrally acting anticholinesterase  in
clinical trials produced good improvement in
memory.
But frequent side effects & Hepatotoxicity restricted
its use.

33. Rivastigmine
Derivative of physostigmine  Reversible AChE
inhibitor  in Ach conc.  Enhance cholinergic NT
Highly lipid soluble  Easily cross BBB
Metabolized by cholinesterase
Has mild peripheral cholinergic side effects
Inhibits cerebral AChE for upto 10 hr
Half life 1.5 hr (P.O.) & 3 hr (Patch)

34. Rivastigmine-Interactions

35. Donepezil
Cerebroselective & Reversible AChE inhibitor 

produces good improvement in cognition in AD.
Therapeutic doses only produces weak peripheral
cholinergic side effects.
 Longer half life  70 hr
Given as once daily dosage (Max 10 mg OD)

36. Galantamine
 Natural alkaloid
Selectively inhibitor of Cerebral AChE
Produced Cognitive & Behavioral benefits in AD
Given as twice daily dosing (Max 12 mg BD)

37. Memantine
NMDA receptor antagonist
It slows down the functional decline
in moderate to severe AD. Memantine
Beneficial effects are also seen in Parkinsonism
Can be given up to 10mg BD
It binds to NMDA receptors, it blocks the effect of
glutamate to protect against acute excitotoxicity
insults in neuronal cells Recovery of AD.

38. MOA of Memantine

39. Piracetam
GABA derivative  Smart Drug
Nootropic action
It selectively improves efficiency of
Telencephalic Integrative activities by
 Enhancement of Learning & Memory.
 Facilitating Synaptic transmission & Inter
hemisphere information transfer.
 Tonic cortical control on subcortical areas.

40. Pyritinol (Pyrithioxine)
Consists of 2 pyridoxine molecules joined by
sulphide bridge  but has No Vitamin Activity
Claimed to Cerebral Metabolism by Glucose
transport
Promoted for Concentration & Memory defects
Head injury
However  Therapeutic benefit is uncertain

41. Piribedil
Dopaminergic agonist
Claimed to Improve Memory, Concentration,
Vigilance, Giddiness & Tinnitus in elderly
patients
But benefits are not substantiated
Minor efficacy in Parkinsonism
Mild G.I complaints

42. Citicoline
 Derived from Choline & Cytidine  It involved in
biosynthesis of lecithin.
 It improve Cerebral function & Enhance cerebral
metabolism
 Short term improvement in Memory & Behavior in
Cerebrovascular disorder patients
 Mainly used in Impaired brain function due to Ischemic
stroke, Parkinsonism & Head injury.

43. Citicoline
Cytidine diphosphate-choline (CDP-Choline)

44. Ginkgo biloba
 Dried extract  Chinese plant
 Contains Ginkgoflavon glycosides
(Ginkgolide B) PAF antagonist
action
 Used in Cognitive & Behavioral
disorders in Elderly
 ADR  On I.V. infusion caused
Fever, Shock & Arrhythmia.

45. References
1. Rationale of Drug of Choice. P Nirmala & N. Chidambaram
2. Lippincott Illustrated Reviews Pharmacology, Karen Whalen,
6th Edt. 2016
3. K. D. Tripathi, Essential of Medical Pharmacology, 8th Edt. 2019
4. BG Katzung & Anthony J Trevor, Basic & Clinical Pharmacology
14th Edt. 2019