This document discusses CNS stimulants and cognition enhancers. It describes various psychomotor stimulants like amphetamines, cocaine, nicotine, and hallucinogens. It discusses their mechanisms of action, effects on the CNS and sympathetic nervous system, therapeutic uses, and adverse effects. It also covers cognition enhancers used for conditions like dementia and Alzheimer's disease. These include cholinergic activators like donepezil and memantine, as well as supplements like Ginkgo biloba. The document provides an overview of how cognition enhancers work to improve brain function and memory.

1. CNS STIMULANTS
&
COGNITION
ENHANCERS
By-VIKAS AAGRAHARI
PHARM-D 2nd yr
DEPARTMENT OF PHARMACY

2. CNS
Stimulants
• Two groups of drugs that act primarily to stimulate the
central nervous system (CNS).
 Psychomotor stimulants
◦ Cause excitement and euphoria.
◦ Decrease feeling of fatigue.
◦ Increase motor activity.
 Hallucinogens (psychotomimetic drugs)
◦ Produce changes in thought patterns and mood.

3. • ◦ Amphetamine
• ◦ Dextroamphetamine
• ◦ Methylphenidate
• ◦ Caffeine
• ◦ Methylxanthines
• ◦ Nicotine
• ◦ Cocaine
Psychomotor stimulants
• ◦ Lysergic acid diethylamide (LSD)
• ◦ Tetrahydrocannabinol
• ◦ Phencyclidine
Hallucinogens

4. Cocaine
• Cocaine is a widely available and highly addictive drug that is currently abused daily by
more than 3 million people in the US.
 MOA:
• Causes blocking of reuptake of monoamines neurotransmitters. So, prolongs their
action.
 Actions:
• CNS: The behavioral effects of cocaine result from powerful stimulation of the
cortex and brainstem. Increases mental awareness and produces a feeling of well-
being and euphoria. Produce hallucinations and delusions of paranoia Respiratory
and vasomotor depression.
• Sympathetic nervous system: cocaine potentiates the action of norepinephrine.
• Hyperthermia.

5. Cocaine
Uses
• Cocaine has a local anesthetic action. For example, cocaine is
applied topically as a local anesthetic during eye, ear, nose,
and throat surgery. [Note: Cocaine is the only local anesthetic
that causes vasoconstriction.]
 Pharmacokinetic
• Self-administered by chewing, intranasal snorting, smoking,
or intravenous (IV) injection. The peak effect occurs at 15 to
20 minutes after intranasal intake of cocaine powder.
• Because the onset of action is most rapid, the potential for
overdosage and dependence is greatest with IV injection and
crack smoking.
• Cocaine is rapidly de-esterified and demethylated to
benzoylecgonine, which is excreted in the urine. Detection of
this substance in the urine identifies a user.

6. Cocaine
 Adverse effects:
• Anxiety
• Depression
• Toxic effects: Cocaine can induce
seizures as well as fatal cardiac
arrhythmias.

7. Methylxanthines
Include theophylline (tea); theobromine (cocoa); and caffeine (coffee, tea,
cocoa, chocolates, cola drinks).
Mechanism of action.
• Translocation of extracellular calcium.
• Increase in cAMP and cGMP caused by inhibition of phosphodiesterase.
• Blockade of adenosine receptors.

8. Methylxanthines
Actions
 CNS-
• Reduces fatigue ad increase mental alertness due to
stimulation of the cortex and other areas of the
brain.
• At very high doses, can produce anxiety and tremor.
• Tolerance to caffeine can develop and withdrawal
consists of feelings of fatigue and sedation.
 Cardiovascular system:
• At high doses, has positive inotropic and
chronotropic effects, can be harmful to angina
patients and can trigger premature ventricular
contractions.
 Diuretic action:
• Caffeine has a mild diuretic effect increasing urinary
output of Na, K, and Cl.
 Gastric mucosa:
• Stimulate secretion of hydrochloric acid from gastric
mucosa, should be avoided in peptic ulcer.

9. Methylxanthines
Therapeutic uses
• All methylxanthines relax the smooth
muscles and Causes relaxation of
bronchioles so use in supportive treatment
of Asthma.
Adverse effects
• Low dose causes insomnia, anxiety, and
agitation.
• A high dosage is required for toxicity, which
is manifested by emesis and convulsions.
• The lethal dose is about 10 g of caffeine
(about 100 cups of coffee), which induces
cardiac arrhythmias; death from caffeine is
thus highly unlikely.

10. Nicotine
 Nicotine is the active ingredient in tobacco. Although this drug
is not currently used therapeutically (except in smoking
cessation therapy), nicotine remains important because it is
second only to caffeine as the most widely used CNS
stimulant, and it is second only to alcohol as the most abused
drug. In combination with the tars and carbon monoxide
found in cigarette smoke, nicotine represents a serious risk
factor for lung and cardiovascular disease, various cancers,
and other illnesses. Dependency on the drug is not easily
overcome.
Mechanism of action:
• 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.

11. Nicotine
CNS stimulant.
Stimulation of sympathetic ganglia increases blood pressure and heart
rate.
Particularly harmful in hypertensive patients.
Nicotine induced vasoconstriction can decrease coronary blood flow,
adversely affecting a patient with angina.
High doses of nicotine result in central respiratory paralysis and severe
hypotension caused by medullary paralysis.
Along with other components of cigarettes like tars and carbon
monoxide, nicotine is a risk factor for lung and cardiovascular diseases
and cancer.

12. Nicotine
Causes dependence that is not easily overcome
Withdrawal symptoms include irritability, anxiety,
restlessness, headaches and insomnia
Smoking cessation programs should combine
pharmacologic and behavioral therapy
Transdermal nicotine patch and nicotine chewing
gum can reduce withdrawal symptoms
Bupropion (Wellbutrin®,
Zyban®)
Antidepressant, can reduce
the craving for cigarettes

13. Nicotine
• Because nicotine is highly lipid soluble, absorption
readily occurs
• Nicotine crosses the placental membrane and is
secreted in the milk of lactating women.
• The acute lethal dose is 60 mg. More than 90 percent
of the nicotine inhaled in smoke is absorbed.
• Clearance of nicotine involves metabolism in the lung
and the liver and urinary excretion.
Pharmacokinetic
• Irritability and tremors, intestinal cramps, diarrhea,
and increased heart rate and blood pressure.
• In addition, cigarette smoking increases the rate of
metabolism for a number of drugs
Adverse effects

14. Amphetamine
 Amphetamine is a non catecholaminergic sympathetic amine. Dextroamphetamine is the major member of this class of
compounds. Methamphetamine is a derivative of amphetamine that can be smoked, and it is preferred by many
abusers.
 MOA
• Releasing intracellular stores of catecholamines.
• Because amphetamine also inhibits monoamine oxidase (MAO), high levels of catecholamines are readily released
into synaptic spaces.
 Action
 CNS: Stimulates the entire cerebrospinal axis, cortex, brainstem, and medulla. This leads to increased alertness,
decreased fatigue, depressed appetite, and insomnia.
 Sympathetic nervous system: Amphetamine acts on the adrenergic system, indirectly stimulating the receptors
through norepinephrine release.

15. Amphetamine
 Uses
• Attention deficit hyperactivity disorder (ADHD): Some young
children are hyperkinetic and lack the ability to be involved in
any one activity for longer than a few minutes.
Dextroamphetamine and Methamphetamine are able to improve
attention and to alleviate many of the behavioral problems
associated with this syndrome
• Narcolepsy: [Narcolepsy is a relatively rare sleep disorder that is
characterized by uncontrollable bouts of sleepiness during the
day]. It is sometimes accompanied by catalepsy, a loss in muscle
control, or even paralysis brought on by strong emotions, such as
laughter. However, it is the sleepiness for which the patient is
usually treated with amphetamine or derivatives of
amphetamine.
 Pharmacokinetic
• Amphetamine is completely absorbed from the gastrointestinal
tract, metabolized by the liver, and excreted in the urine.
• Amphetamine abusers often administer the drugs by IV injection
and by smoking.
• The euphoria caused by amphetamine lasts 4 to 6 hours, or four-
to eight-fold longer than the effects of cocaine.

17. HALLUCINOGENS
Psychotomimetic drugs, that induce
altered perceptual states
accompanied by visions of bright,
colorful changes in the environment.
These drugs impair normal decision-
making because they interfere with
rational thought.

18. HALLUCINOGENS
 Lysergic acid diethylamide (LSD)
• Serotonin agonist.
• Activation of the sympathetic nervous system
occurs causing pupillary dilation, increased
blood pressure, and increased body
temperature.
• Taken orally, low doses of LSD can induce
hallucinations with brilliant colors.
• Haloperidol and other neuroleptics can block
the hallucinatory action of LSD.
 Adverse effects
• Hyperreflexia, nausea, and muscular weakness.
• High doses may produce long-lasting psychotic
changes.

19. HALLUCINOGENS
• Tetrahydrocannabinol
• Found in marijuana
• Produce euphoria followed by
drowsiness and relaxation
• This product is prescribed to treat
emesis and to stimulate the appetite.
• Its wide range of effects includes
appetite stimulation, xerostomia, visual
hallucinations, delusions, and
enhancement of sensory activity.

20. Tetrahydrocannabinol
 Adverse effects include:-
• increased heart rate
• decreased blood pressure
• reddening of the
conjunctiva.
At high doses, a toxic psychosis
develops.

21. HALLUCINOGENS
Phencyclidine
• Illegal drug.
• Also known as PCP or angel’s dust.
• Inhibits the reuptake of dopamine, 5-HT, NE.
• Produces numbness of extremities, staggered gait,
slurred speech, and muscular rigidity.
• At increased dosages, anesthesia, stupor and coma
may result.
• Increased sensitivity to external stimuli results, CNS
actions may persist for a week.
• Tolerance often develops with continued use.
• No therapeutic applications.

22. Cognition Enhancers
(cerebroactive drugs)

23. What is
cognition?
• In simple terms it is the Brain process of acquiring and exploiting
knowledge.
• Mental processes involved in gaining knowledge and
comprehension, including thinking, knowing, remembering,
judging and problem-solving
– higher-level functions of the brain and encompass language,
imagination, perception and planning
Multiple levels of Neurobiological process –
learning, memory, attention and motivation
Hippocampus– encoding new information
Strio-frontal circuit– decision making
Frontal lobe - retrieval
• Cognition Enhancers are the drugs used in the disorders of these
functions
– Amnesia Alzheimer`s Disease

24. What is Dementia?
 Deterioration of intellectual faculties, such as memory, concentration,
and judgment to previously unimpaired person.
Lost: Memory, capacity to solve problems of day to day, learned motor
skills, social skills, control of emotions.
Retained: Consciousness and motor functions.
 Causes:
o Aging
o Alzheimer`s Disease
 Most common cause of dementia.
 Progressive neurodegenerative disorder of older
individuals leading to a total vegetative state.
 Atrophy of cortical and subcortical areas with
deposition of amyloid protein in the form of senile
plaques - marked cholinergic deficiency.
o TIA, CVA and stroke etc.

25. Classification
Cholinergic
activators
Tacrine,
Rivastigmine,
Donepezil,
Galantamine
Glutamate (NMDA)
antagonist: Memantine
Miscellaneous
Piracetam,
Pyritinol,
Dihydroergotoxi
ne, Piribedil,
Ginko biloba
Herbs and
Nutrients

26. How do they
work?
– They are believed to act by:
Increasing Blood Flow
Increased Brain
 Neurotransmission Enhancement
 Increased Neuronal metabolism
 Stimulation of Hormones and
Enzymes
 Increased Nerve growth
– Improvement of Cerebral Functions -
Memory

27. Ginko biloba
• – Ginko meaning naked
• – Maidenhair Tree - Chinese and Japanese plant
• – Contains ginkgoflavon glycosides – PAF antagonist
• – Used in a variety of cognitive and behavioural disorders in Elderly
• – Prevents cerebral impairment in Multiple infarct disease (MID)
• – ADRs: GIT upset and arrhythmia etc.
• – Doses: 40 mg tds for 4 weeks
• – Preparations: Ginkocer, Bilovas, Ginkoba
• – Efficacy is doubtful – also used with Gotu Kola (Brahmi)