This document discusses several central nervous system (CNS) stimulants. It describes how Parkinsonism involves slowed movement and tremors, and can be treated with drugs that increase dopamine like levodopa. Alzheimer's disease causes dementia and memory loss, and is treated with cholinergic drugs. CNS stimulants temporarily improve mental and physical function and include xanthines like caffeine, amphetamines, and methylphenidate. Other stimulants discussed are pentylenetetrazol, nikethamide, strychnine, and lobeline.

1. :
DRUG USED IN PARKINSON &
ALZHEIMERS DISEASE ,
CNS STIMULANT
1

2. Parkinsonism is a progressive neurological disorder
of muscle movement as a clinical syndrome
consisting of 4 cardinal features:
• Bradykinesia (slowness of movement) and, in
extreme cases, a loss of physical movement
(akinesia)
• Muscular rigidity
• Resting tremor (which usually disappears during
voluntary movement) 6)impairment of postural
balance leading to disturbances of gait and falling2

3. 1 ) Drug that increase dopamine content
ex. levodopa, combination of levodopa with
a) Dopa-decarboxylase inhibitors
ex. carbidopa and benserazide
b) Inhibitors of MAO-B
ex. selegalline
c) COMT Inhibitors
ex. entacopone
2) Dopamine receptor agonist
ex. Bromocriptine 3

4. 3) Drug that releases dopamine
ex. Amantadine
4) Cholinergic antagonisty
ex. Benztropine,trihexyphenidyl
5) Antihistamines
ex. Diphenhydramine
4

5. • Levodopa is (the most effective drug used in the treatment of
parkinsonism)
Chemistry: • It is the metabolic precursor of dopamine
Mechanism of action:
• In the brain, levodopa is converted to dopamine by decarboxylation
primarily within the presynaptic terminals of dopaminergic neurons
in the stratium (by action of L-aromatic amino acid decarboxylase).
The dopamine produced is responsible for the therapeutic
effectiveness of the drug in PD; after release, it is either transported
back into dopaminergic terminals by the presynaptic uptake
mechanism or metabolized by the actions of MAO and catechol-
Omethyltransferase (COMT) .
5

6. • If levodopa is administered alone, the drug is
largely decarboxylated by enzymes in the
peripheral sites so that little unchanged drug
reaches the cerebral circulation.
• In addition, dopamine release into the
circulation by peripheral conversion of
levodopa produces undesirable effects,
6

7. levodopa is rapidly absorbed by an active
transport ,decrease in gastric emptying time
and low pH decreases absorption the peak
effect is raised in half an hour.
Half life of levodopa is 1-
3 hours ,about 95% of levodopa metabolized
peripherly and only 1% cross blood brain
barrier excretion occurs through kidney as
homovanillic acid
7

8. • Alzheimer disease is one of the most common
neurodegenerative disorder amongst the
elderly leading to dementia it refers to several
illnesses which affect the functioning of the
brain leading to destruction in memory
reasoning
Clinical symptoms of Alzheimer's disease
• Early stage : Recent memory loss beginners
confusions about places things work loses
initiative poor judgement. 8

9. • Middle stage : Increasing memory loss
problems recognizing the friend or family
members occasionally muscle twitches or
jerking can't find right words
• Late stage : Can't recognize family or image
of self at mirror lose weight even with diet
can't control my bladder may have seizures
9

10. Drug used are
• Earlier for the loss of memory drugs that
improve blood flow or psychostimulators like
amphetamines, pentoxifylline were tried.
• Use of glutamate receptor agonist or
potentiators like piracetam,aniracetam were
introduced as nootropics or memory enhancing
drugs.
• Decrease in cholinergic mechanism in
Alzheimer disease lead to use of cholinergic
drugs. 10

11. Drugs……
a) Precursors of Ach synthesis :
Choline chlorides lecithin (Phosphatidylcholine)
b) Cholinergic receptor agonist ex. Bethenechol
c) Anti-cholinesterase ex.
physostigmine,tacrine,doneprazile,galantamine.
11

12. 12

13. • CNS consist of Brain and Spinal cord, and serves to
coordinate and direct all body functions.
• Homeostasis is control by CNS. Compounds that
increase an initial low level of physiological activity are
generally classified as CNS stimulant.
• CNS stimulants are the psychoactive drugs that induce
temporary improvement in either mental or physical
function or both
• CNS stimulants are used as analeptics that is picking up
those who have been cast down the street respiratory
centres and other systems
13

14. 1) Those acting directly on CNS are
a) Predominantly cortical stimulants : ex.
Xanthine alkaloids, amphetamines,
methylamphetamines, methylphenidate and
pipradrol.
b) Predominant medullary stimulants : ex.
picrotoxin,pentylenetetrazole,nikethamide,ami
phenazole camphor and carbon dioxide
14

15. c) Predominantly spinal stimulants :
ex: Strychnine
2) Those, which stimulate the central nervous
system reflexively : ex
lobeline,ammonia ,veratrum and nicotine.
15

16. • They act on the central nervous system and provide a
temporary sense of alertness and well being as well as
relief from fatigue.
Xanthine alkaloid :
The three naturally occurring
caffeine,theophylline,theobromine are purine bases which
occur in several plants all over the world. They share in
common several pharmacological action of therapeutic
interest.
• They relax smooth muscle,notably bronchial muscle,
CNS stimulant ,cardiac muscle and act on kidney as a
diuretic. 16

17. • Various beverages, particularly tea, coffee and cocoa, contain
methylxanthines, to which they owe their mild central stimulant
effects. (theophylline, caffeine, theobromine) are the drugs
included in metylxanthines.
• Mode of action :
Methylxanthines (especially theophylline) inhibit
phosphodiesterase, which is responsible for the intracellular
metabolism of cAMP. They thus increase intracellular cAMPand
produce effects that mimic those of mediators that stimulate
adenylyl cyclase.
Methylxanthines also antagonise many of the
effects of adenosine, acting on both A1 and A2 receptors. 17

18. Clinical use :
Use with aspirin in some preparations for treating
headaches and other aches and pains,
• Theophylline (formulated as aminophylline) is used
mainly as a bronchodilator in treating severe
asthmatic attacks.
Side effects :
• High doses of caffeine cause epileptiform type of
convulsion ,nervousness,insomnia, tremors.
18

19. • Its a non catecholamine, (shows neurologic and
clinical effects quite similar to those of cocaine).
Dextroamphetamine is the major member of this class
compounds methamphetamine (speed) is a derivative
of amphetamine that can be smoked and it is
preferred by many abusers.
• Mechanism of action: Amphetamine, act by
releasing intracellular stores of catecholamines. Also
inhibits MAO, high level catecholamines are readily
released into synaptic spaces.
19

20. a. CNS: The major behavioral effects of
amphetamine result from a combination of its
dopamine and NE release enhancing
properties.Amphetamine stimulates the entire
cerebrospinal axis, brainstem, and medulla.
This leads to increase alertness, decrease
fatigue, depressed appetite, and insomnia.
b. Sympathetic Nervous System: indirectly
stimulating the receptors through NE release.
20

21. It has CNS stimulant properties similar to those
of amphetamine and may also lead to abuse.
Methylphenidate is a more potent dopamine
transport inhibitor than cocaine, thus making
more dopamine available.
It has less potential for abuse than
cocaine, because it enters the brain much more
slowly than cocaine and, does not increase
dopamine levels as rapidly.
21

22. • Methylphenidate is a dopamine transport
inhibitor and may act by increasing dopamine
in the synaptic space.
• Used for ADHD in children.
22

23. 23

24. • They are also called as analeptics
• Analeptics are general CNS stimulants,they
stimulate vitally important centers (respiratory
and vasomotor) of the brain.
• The primary medical use of these drugs is as
an anesthetic recovery tool or to treat
emergency respiratory depression,hence they
are also called as repiratory stimulant.
24

25. Also called cocculin is a poisonous crystalline
plant compound
• Acts as a non competitive channel blocker for
GABA receptor chloride channels
• It have stimulant & Convulsant effect
25

26. • Pentylenetetrazol, also known as
pentylenetetrazole, metrazol, pentetrazol
(INN), pentamethylenetetrazol, Corazol,
Cardiazol or PTZ, is a drug formerly used as a
circulatory and respiratory stimulant.
• MOA : It is specifically a GABA-a receptor
antagonist it acts at the picrotoxin (PTX) site
of the gamma-aminobutyric acid type A
(GABA(A)) receptor.
26

27. Mechanism of action:
Nikethamide was formerly used as a
respiratory stimulant but its use for this
indication is no longer recommended as the
effective doses are close to those causing toxic
effects (especially convulsions).
27

28. Pharmacological effects:
• Acting as antidote for barbiturate overdose.
• Increasing the behavioral alertness.
Side effects:
• Skin irritation.
• Eye irritation.
• Respiratory irritation.
28

29. 29

30. • Strychnine is a naturally occurring alkaloid found
in seeds from the plant Strychnos noxvumica
Site of action : Spinal cord
Mecahnism of action :Strychnine is an antagonist
of glycine, Strychnine competitively and
reversibly the inhibitory neurotransmitter, glycine
at postsynaptic neuronal sites in the spinal cord
30

31. 31

32. Mechanism of action:
• Low dose: Ganglionic stimulation.
• High dose: Ganglionic blockade.
Pharmacological effects:
• CNS( low dose): euphoria, arousal and relaxation,
improvement of attention, learning , reaction time.
• CNS( high dose): respiratory and medullary paralysis.
• CVS: increase heart rate, blood pressure,
vasoconstriction.
• GIT: increase motility, secretions. 32

33. Adverse effects:
• Low dose: Irritability,tremors,addiction.
• High dose: Palpitaions,hypertension,intestinal
cramps.
33

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