JULY

CNS STIMULANTS
2021

&
NOOTROPIC
AGENTS

DR. A. R. VIJAYAKUMAR
 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
CNS STIMULANTS
 CNS Stimulants
 Drugs which elevate Mood, Increase feelings of well-being,

Increase energy & Alertness & Suppress appetite  CNS

Stimulants.
 CNS Stimulants

 Drug cause Excitement, Euphoria, Decrease feeling

of

fatigue & Increase motor activity 

Psychomotor Stimulants.

 Drug which affect Thought, Perception & Mood



Hallucinogens or Psychomimetics.
 Classification
CNS Stimulants

RESPIRATORY PSYCHO
CONVULSANTS
STIMULANTS -STIMULANTS

AMPHETAMINES
METHYL PHENIDATE
STRYCHNINE
ATOMOXETINE
PICROTOXIN
MODAFINIL
BICUCULLINE DOXAPRAM
ARMODAFINIL
PENTYLENETETRAZOL NIKETHAMIDE*
PEMOLINE*
COCAINE
CAFFEINE
NICOTINE*
 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
 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.

 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

 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.
 Bicuculline
 Synthetic Convulsant has Picrotoxin like action

Competitive GABAA receptor antagonist

 Research purpose
 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
 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.

 Psychomotor Stimulants -
Amphetamines
 Indirect sympathomimetics  neuron to
Adrenergic release NA
 Similar pharmacological profile to Ephedrine
 It potent CNS stimulant & peripheral
weaker
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
 Amphetamine
 Central s by release of NA from adrenergic
action neurons in
 brain
By diffusion & reverse transport involving
exchange like Norepinephrine transporter
transporters transporter (DAT) & Vesicular monoamine
Dopamine (NET),
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
 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
 Methylxanthines

Caffeine, Theophylline & Theobromine:

 Coffee  Caffeine

 Tea  Theophylline & Caffeine

 Cocca  Caffeine & Theobromine

 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.
 Caffeine
Pharmacological action:

 Kidneys  Diuretic
effects

 Smooth muscles 
Relaxation (Bronchial
SM)

 Skeletal muscles
 Enhance the
power of
 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

 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
 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

 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
ROA of CNS Stimulants
 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.

 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

 Methylphenidate
 Chemically similar to Amphetamine

 Well absorbed orally & given twice daily

as dosage

 Acts by releasing NA & DA in brain

 It is superior to Amphetamines for treatment

of Hyperkinetic children (ADHD)

 Modafanil
 Popular with night shift (call centre) workers
&
others who want to improve & keep
alertness 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.
NOOTROPIC
AGENTS
 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
 Classification
Nootropic Agents

CHOLINERGIC GLUTAMATE MISCELLANEOUS

ACTIVATORS ANTAGONIST

TACRINE MEMANTINE PIRACETAM

RIVASTIGMINE PYRITINOL

DONEPEZIL DIHYDROERGOTOXINE

GALANTAMIN CITICOLINE

E PIRIBEDIL

GINKGO BILOBA
 Cholinergic
 Since, Activators
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.
 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)

Rivastigmine-Interactions
 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)

 Galantamine
 Natural alkaloid

 Selectively inhibitor of Cerebral AChE

 Produced Cognitive & Behavioral benefits in AD

 Given as twice daily dosing (Max 12 mg BD)

 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.
MOA of Memantine
 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.
 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
 Piribedil
 Dopaminergic agonist

 Claimed to Improve Concentration,

Memory,
Tinnitus in elderly
Vigilance, Giddiness &
patients

 But benefits are not substantiated

 Minor efficacy in Parkinsonism

 Mild G.I complaints

 Citicoline
 Derived from Choline &  It involved in
Cytidine

biosynthesis of lecithin.
Enhance cerebral
 It improve Cerebral function
&

 metabolism
Short term improvement in Memory & Behavior
in

Cerebrovascular disorder patients

 Mainly used in Impaired brain function due to

Ischemic stroke, Parkinsonism & Head injury.

 Citicoline

Cytidine diphosphate-choline (CDP-Choline)

 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.

 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