complete explanation with amicable pictures regarding CNS stimulants and cognitive enhancers.useful for both UG and PG students.references from different books and authors

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CNS STIMULANTS
&
COGNITIVE ENHANCERS

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3. CNS STIMULANTS
The CNS stimulants mostly produce a generalized
action which may, at high doses, result in
convulsions.
They are 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) and sometimes lead to death in over
dose.

5. CLASSIFICATION
1. Convulsants: Strychnine,Picrotoxin,Bicuculline,
Pentylenetetrazol (PTZ).
2. Analeptics(respiratory stimulants): Doxapram
3. Psychomotor stimulants: Amphetamines,
MDMA,DEXAMPHETAMINE,Methylphenidate
Atomoxetine,Modafinil,Armodafinil,Sibutramine
Pemoline, Cocaine,
Caffeine.
 Many other drugs are capable of causing CNS
stimulation as side effect or at high doses.

6. CONVULSANTS

7. CONVULSANTS
1. Strychnine: It is an alkaloid from the seeds of
Strychnos nux-vomica,and a potent convulsant.
Example Strychnine (30mg)
Site of
action Spinal cord.(stimulant)
MOA
Block the postsynaptic inhibitory
response to glycine by blocking glycine
receptors. Glycine is the main inhibitory
transmitter acting on motor neurons.
End point
Tonic convulsion.( slow IV diazepam/clonazepam

8. Opisthotonus Also seen in;
•Cerebral
palsy
•Traumatic
•Brain injury
-tetanus

11. 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.

12. Examples Picrotoxin (20mg)
Site of
action
Medulla oblongata.
MOA
1.It inhibits the presynaptic
inhibition→decrease GABA.
2.Non-competitive GABAA
receptors blocker which is a
chloride channel blocker.
End point
Clonic convulsions
hyperpolarisation-excitation.
Treatment Symptomatic (diazepam)

14. BICUCULLINE :
• This synthetic convulsant has picrotoxin
like actions.
• It is a competitive GABA-A receptor (intrinsic
Cl¯ channel receptor) antagonist.
• NO CLINICAL USE
• It is only a research tool.

15. Dicentra cucularia

16. PENTYLENETETRAZOL (PTZ)
laptazol, metrazol
It is a powerful CNS stimulant
Low doses cause excitation, larger doses produce
Convulsions
Antagonism of PTZ induced convulsions is an
established method of testing anticonvulsant
drugs in laboratory animals
DOC :- diazepam/clonazepam.

17. ANALEPTICS

18. ANALEPTICS (Respiratory stimulants)
These are drugs which stimulate respiration and can
have resuscitative value in coma or fainting.
Mechanical support to respiration and other
measures to improve circulation are more effective
and safe.
Low doses they are selectively act on resp center
Inc depth of breathing by acting on resp center in
medulla

19. Situations in which analeptics may be employed
are:
(a) As an expedient measure in hypnotic drug
poisoning untill mechanical ventilation is
introduced.
(b) Suffocation on drowning, acute respiratory
insufficiency.
(c) Apnoea in premature infant.
(d) Failure to ventilate spontaneously after
general anaesthesia.

20. Doxapram:
It acts by promoting excitation of central
neurons.
At low doses it is more selective for the
respiratory centre.
Respiration is stimulated through carotid and
aortic body chemoreceptors.
Continuous i.v. infusion of doxapram may abolish
episodes of apnoea in premature infant not
responding to theophylline.

21. Uses :
 Post-anaesthetic resp. depression
 COPD i.e. hypoxemic, hypercapnic res.failure.
 Apnoea in premature infants
Dose- 2-5mg/min(max 4mg/kg) slow i.v infusion.
Contraindications:
 Resp.fail due to neurological & muscular
diseases.
 Epilepsy
Side effect:
 Restlessness, Tachycardia
 High doses: convulsions & arrhythmias

23. PSYCHO
STIMULANTS

24. PSYCHOMOTOR STIMULANTS
Amphetamine group:
 Amphetamine
 Dexamphetamine
 Methamphetamine
 Methylenedioxy Methampheta(MDMA)
 Methylphenedate
 Fenfluramine

25. Non-Amphetamine group
 Modafinil
 Atomoxetine
 Sibutramine
 Pemoline
Cocaine
Methylxanthines:
 Caffeine
 Theophylline
 Theobromine

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 PSYCHOMOTOR STIMULANT.
 DERIVATIVES:
DEXAMPHETAMINE,METHAMPHETAMINE,MDMA.
 EFFECTS:
MOTOR ACTIVITY
EUPHORIA
ANOREXIA
EXCITEMENT
REDUCED FATIGUE.
STEREOTYPED AND PSYCHOTIC BEHAVIOUR.
INCREASE IN SEXUAL DRIVE.
OTHER NAMES: SPEEED, BILLY WIZZ, POORMANS COCAINE
AMPHETAMINE

27. PSYCHOMOTOR STIMULANTS
Amphetamine & Non- Amphetamine:
MOA:
 Drug enter N endings by active transport
 Displace DA(also NE) from vesicles by altering pH
 ↑DA conc. In synaptic cleft
 Also inhibits MOA-B, ↓DA metabolism & DA
 Release to synaptic cleft by reverse transport

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29. PERIPHERAL EFFECTS
 ↑ BP,inhibition of GI motility
 Fatigue both physical & mental reduced.
 Amphetamine psychosis on repeated use-
hallucinations.(NO VISUAL)
AGGRESIVENESS ON OVER DOSAGE.
PK:
 Well absorbed orally
 Freely penetrates BBB
 Unmetabolised drug excreted in urine

31. USES
ADHD with minimal brain dysfunction:
 Characterised by-
 Hyperactivity
 Inability to concentrate
 Impulsive behavior
Dexamphetamine,
Methylphenedate,
Atomoxetine quite effective.

33. Narcolepsy: Characterised by-
 Sleep attacks during day time
 VIVID Night mares in awakening state
CATAPLEXY (loss of muscle tone).
Methylphenedate is still used
Modafinil- used successfully.
devoid of abuse liability

35. APPETITE SUPPRESSION
 Fenfluramine, dexfenfluramine used earlier to
treat obesity
Discouraged due to:-
 Tolerance
 Insomnia, Pul.HTN, Abuse potential.
Sibutramine new drug used now
 Blocks neuronal uptake of mainly NE & 5HT
(also dopamine) at hypothalamic site that
regulates food intake.

36. Use:
 Severe obesity with risk factors like DM.
Adverse effects:
 Dry mouth
 Headache
 Insomnia
 Constipation
 ↑in HR & BP
 CI in CVS diseases, withdrawn from market

37. ADVERSE EFFECTS
 Tolerance
 Psychic dependence, rarely physical.
Amphetamine overdose:
 Euphoria, dizziness, tremors, HTN
Irritability, anorexia, insomnia
 Higher doses- convulsions, psychotic
manifestations, arrhythmias, coma

38. • Aamphetamine toxicity treated with DIAZEPAM (SLOW IV)
• FOR PSYCHOTIC AGITATION – HALOPERIDOL
• GASTRIC LAVAGE
 Acidification of urine by administering AMMONIUM CHLORIDE &
ASCORBIC ACID. This increase elimination of amphetamine in urine.
 Anti-hypertensive drugs like – LABETOLOL
 For ARRYTHMIAS - ESMOLOL
Treatment typically requires more than one year of Intense intervention
consisting of drug abstinence,cognitive, emotional and motivational
rehabilitation.
Treatment Of Acute Poisoning
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39.  also called ECTASY. (love drug)
INDUCES THE RELEASE OF NE,DA
Induces heat stroke like condition-
rhabdomyolysis & renal failure
Methamphetamine = meth
75mg- psychotomimetic effects
150 mg-LSD like effects
300mg- amphetamine like
 SE: tachycardia, HTN, arrhythmias
aphrodisiac, euphoriant
MDMA=methylenedioxy methamphetamine

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43. History of Cocaine
SIGMUND FRAUD USED COCAINE FOR
TREAT DEPRESSION.
ALBERT NEIMANN
from coca leaves.
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44. What is it?
Pure cocaine was first isolated from the leaves of the coca
bush in 1860.
Contained in small amounts in the leaves of
ERYTHROXYLUM (coca) bush
Researchers soon discovered that cocaine numbs whatever
tissue it touches.
This lead to it’s use as a local anesthetic.
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45. Where does it come
Coca leaves grow on the slopes of the Andes
Mountains.
For at least 4,500 years, people in Peru & Bolivia have
chewed the coca leaves to lessen hunger & fatigue.
Most of the world’s supply of coca is grown & refined
into cocaine in Colombia.
HIGHEST ABUSE LIABILITY.
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46. How is it used
SNIFFED (15 – 30 min)
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SMOKED
(5-10 min)
INJECTED
3min

47. Cocaine
Pharmacodynamics
Indirect Agonist for
DA (high affinity)
NE (high affinity)
5-HT (modest affinity)
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• Mechanism:
– Blocks monoamine
reuptake

48. Short-term effects
Dilated pupils
Increased body temperature, Blood pressure & heart rate
Insomnia
Loss of appetite
Increased energy
Reduced fatigue
Mental clarity
Talkativeness
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49. Long-term effects
Paranoia
Depression
Ulcers in the membranes of the nose
Dulled senses of taste & smell
Weight loss, poor health & sexual dysfunction
Loss of social & financial supports
Holes in bony separation between nostrils in nose
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51. COCAINE+ HEROIN
Concurrent or substitute use
Multiple drug use (nicotine, alcohol, heroin,
amphetamines, hallucinogens).
Cocaine + heroin => “speed ball”
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52. PHARMACOTHERAPIES
Treatment of withdrawal:
Alpha-blockers
Chlorpromazine: DA antagonist (also blocks alpha receptors)
Haloperidol (antipsychotic – 50x more potent than
chlorpromazine).
Alprazolam (Xanax - benzodiazepine) for panic attacks.
Antidepressants (fluoxetine or desipramine).
Diazepam (Valium) for seizures
AMANTIDINE for withdrawl effects of cocaine.
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 Cocaine is known to have a number of effects
during pregnancy.
 elevated risk of placental abruption
 Due to its vasoconstrictive and hypertensive
effects, they are also at risk for haemorrhagic
stroke and myocardial infarction.
 Cocaine is also teratogenic it can cause birth
defects and foetal malformations.
 cocaine babies
COCAINE IN PREGNANCY

54. METHYLXANTHINES
 Only caffeine if used as CNS stimulant
PK:
 Oral- rapid but irregular absorption
 PPB:<50%
 Distributed all over the body
 Metabolism: in liver by demethylation & oxid.
 Metabolites excreted in urine
 T1/2: 3-6hrs

57. AE:
 Gastric irritation, Nause, Vomiting.
 Nervousness, insomnia, agitation
 Muscule twitch, rigidity
 ↑body temp, delirium, convulsions
 Tachy, extra systoles at high doses
Uses:
 In Analgesic mixture for headache
 Migraine
 Apnoea in premature infants

58. PSYCHOTOMIMETIC
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 LYSEGIC ACID DIETHYLAMIDE
 MESCALINE
 PHENCYCLIDINE
 CANNABINOIDS
 Molecular target- 5-HT2AR – Gq receptor
 Hallucinogens

59. LYSERGIC ACID DIETHYLAMIDE
 Derived from cereal fungus ergot
 Hofmann synthesized & experimented on himself.
 Act as agonist at 5HT2 receptors.
suppress electrical activity in sertoninergic raphe
 Excitation threshold of retina ↓- visual
hallucinations, hyper arousal state
 Experiences may be bad or good trip.
psychedelic effects with 1μg/kg.
trips lasting for 6-12 hours.
experience flashbacks at any time.

61. Mescaline
Mescaline – A hallucinogen obtained from a
small spineless cactus Peyote.
From earliest recorded time, peyote has been used by natives in
northwestern Mexico and the southwestern United States as a
part of traditional religious rites.
The drug is usually taken orally, without chewing, although it can
still be smoked, or even injected.
It’s chemical structure is close to that of an amphetamine
(stimulant).
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62. PSILOCYBIN MUSHROOMS
How are they taken?
Eaten raw
Cooked in food
Brewed in tea
Dried and ingested
Street names:
Magic mushrooms
“Shrooms”
How long does a trip last?
5-6 hours
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63. Psilocybin Mushrooms Effects
Nausea
Dilated pupils
Tightness in the neck
• Induce sensory hallucinations
• Hear things that are not real
Effects caused by shrooms begin about 30 min.
after consumption and last nearly 5 hours.
During this period, laughing is somewhat uncontrollable
and visual hallucinations caused by organic objects are
typical.
Psilocybin acts by affinity to serotonin 5-HT receptors.
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65. CANNABINOIDS
 Cannabis Sativa (Hemp)
Cannabis indicia
 GATEWAY DRUG
Psychoactive agent = ∆9 Tetrahydocannabinol (THC)
Found in all parts of the plant, but concentrated in the
sticky resin secreted from the flowing tops of ♀ plants.
WORLDS MOST POPULAR DRUG OF ABUSE
 The herb was called GANJIKA in Sanskrit
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66. HASH OIL:
It obtained by extracting THC from Hashish or
Marijuana in oil.
 Clear pale yellow / green
to brown black colour.
 THC concentration 15-30%.
GANJA: Buds and flowering top of
female plant.
BHANG: Cut and dried large
leaves & stem of plants. 6
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MARIJUANA
- Dried and crumbled leaves, small
stems, flowing tops of the plant
- Usually smoked in joints,
pipes, bongs,
- also called grass,
pot,weed,reefer.
- THC content varies…
SINSEMILLA:
pollination prevented (↑ potency)
The Gang Bong: The 4 barrel brain blaster!

68. MECHANISM OF
ACTION
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69. Common Routes- CANNABINOIDS
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 Smoking
 Oral ingestion
 Cannabis tea
 Cannabis+alcohol = green dragon

70. PHARMACOLOGY OF CANNABIS
 11- hydroxyl ∆9-THC.(active form)
 Typical Joint contains approximately 0.5 – 1g of cannabis
- If THC content = 4%... joint with 1g of cannabis contains 40 mg of
THC
 Burning marijuana results in vaporisation of THC→ absorption
into the lungs
 Only about 20% of original THC is absorbed:
Breathing isn’t optimal –
can be increased by breath holding
Increased high with 15 s breath hold vs. 7 s
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71. ACTIONS - CANNABIS
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DURING SEDATIVE PHASE: IMPAIRED CONCENTRATION
LSD LIKE EFFECTS
IMPAIRED SHORT TERM MEMORY
-
DURING STIMULATORY PHASE:
EUPHORIA
TALKTIVENSS, APPETITE
FEELING OF WELL-BEING
MOOD TRIPS WILL BE SEEN.
PERIPHERAL EFFECTS: TACHYCARDIA
BLOODSHOT EYES
IOP
BRONCHODILATATION
AMOTIVATION SYNDROME.
RUNNING AMOK CHRONIC POISONING

72. MOA, USES
 Two types CB 1& 2 receptors
 CB1 in brain CB2 in periphery
 Anandamide-endogenous ligand CB1.
 Dronabinol, Nabilone- synt.analogues of THC
 Use: CB1 Agonists- ↑appetite in AIDSpts.
 Dronabinol-antiemetic in cancerchemo.
 Rimonabant : CB1 antagonist, used for obesity,
dose-20mg OD before Breakfast
 Smoking cessation

73. COGNITIVE
ENHANCERS

74. COGNITION ENHANCERS
Cognition is "the mental action or process of
acquiring knowledge and understanding through
thought, experience, and the senses.“
It encompasses processes such
as knowledge, attention, memory and working
memory, judgment and evaluation, reasoning an
d "computation", problem solving and decision
making, comprehension and production
of language,

75. COGNITION ENHANCERS
Indications:
 AD, multi infarct dementia
 Mild cognitive impairment
 learning defects, ADHD in children
 CVA, Stroke,TIA
 Organic psychosyndromes
 Sequale of head injury
 ECT, brain surgery

76. MECHANISMS
 ↑ global/regional blood flow(CBF)
 Direct support of neuronal metabolism
 Enhancement of neurotransmission
 Improvement of discrete cerebral functions
(memory)

77. ALZHEIMERS DISEASE
 Main pathological features:
 Amyloid plaque
 Neurofibrillary tangles
 Marked ↓ in choline acetyltransferase & loss
of cholinergic neurons in brain.

78. CHOLINERGIC ACTIVATORS
 ACEs that cross BBB are preferred.
Tacrine:
 Longer acting, reversible ACE
 Palliative for mild to moderate AD
 Orally active
 Improves memory, cognition, well being
 Facilitates Ach release
 AE: hepatotoxicity

80. DONEPEZIL, RIVASTIGMINE & GALANTAMINE
 Newer reversible Anti cholinesterase
 Better penetration in to CNS(lipid soluble)
 Better tolerated & less toxic than tacrine
 Clinical results modest & temporary
 Donepezil: 5mg OD orally evening ↑ max
10mg after 4 wks
 Rivastigmine:1.5 mg orally BD ↑ to 3mg BD
after 2 wks upto max 6mg/BD.
 Galantamine:4mg BD orally ↑to 8mg BD after
2 wks

81.  Transdermal Rivastigmine patch –applied
every 24hrs
 SE:diarrhoe, N, V, ↑urination
Acetyl-L-carnitine:
 Structural analogue of Ach
 ↓ signs & symptoms of dementia in AD
 ↑ cholinergic transmission
 Also have antioxidant properties, slows
progression ofAD

82. MEMANTINE
 Excitotoxicity due to enhanced Glutamate
transmission via NMDA recp.
 Dose:5mg OD slowly ↑ to 10-20mg/day
 Non-comp. antagonist of NMDA recp.
 Better tolerated, less toxic.
Miscellaneous :
 Nootropics- piracetam, aniracetam
 High doses of vit E(1000 IU B.D)
 Antioxidants-vit C, A, Zn, Se, bioflavonoids or
spirulina ↓ progression even in middle stage
AD.

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PIRACETAM
MOA:-
↑ ACh activity in the brain
↑ glutamate activity via AMPA and NMDA receptors
~ improve membrane permeability of neurons→ enhances overall
neuronal function.
USE :-
Cognitive impairement & Dementia in elderly, ADHD.
DOSE:-
0.8-1 gm TDS, Oral
1-3 gm, i.m, 6th hrly.

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Natural Nootropics:-
Bacopa monnieri (Brahmi):
• Enhancement of PK activity, protein synthesis in
hippocampus
• Natural antioxidant & DNA damage preventing agent
•Anti stress property
• It enhances memory and intellect.

86. 86ASHWAGANDHA:
 Indian GINSENG
 Anti oxidant properties
 Neuronal regeneration : Which helps in
Neuro degenerative disorders.
 Extract inhibits AchE enzyme.

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Ginkgo biloba:
 Neuro protective effects
Antioxidant, Anti apoptotic, Anti amyloidogenic properties
Used in Alzhiemer’s disease , other cognitive disorders.
Panax Ginseng (king herb):
 Chinese traditional medicine
Antioxidant property
Release of neurotransmitters in the brain

88. THANK YOU