This document discusses central nervous system stimulants and nootropics. It describes various classes of CNS stimulants like amphetamines and analeptics. Amphetamines produce euphoria and wakefulness but can have side effects like rapid heart rate and high blood pressure. Caffeine is discussed in depth, with its mechanisms of action and effects on exercise performance. Other cognitive enhancers mentioned include racetams, citicoline, and herbs. The document also covers potential adverse effects of CNS stimulants like restlessness, convulsions, and cardiac issues.

1. CNS Stimulants
& Nootropics
KRVS Chaitanya

2. Central Nervous System Stimulants
Central Nervous System Stimulants
– Analeptics: invigorating/restorative drugs (tx
asthma/COPD)
– Amphetamines: produce euphoria/wakefulness (care less
about pain/tiredness)
– Anorexiants: suppress the appetite (weight-loss – w/
healthy diet and exercise)

3. Classification
1. Convulsants
– Strychnine, Picrotoxin, Bicuculline, Pentylenetetrazol
(PTZ).
2. Analeptics: Doxapram
3. Psychostimulants
– Amphetamines, Methylphenidate, Atomoxetine, Modafinil,
Armodafinil, Pemoline, Cocaine, Caffeine.
• Many other drugs are capable of causing CNS
stimulation as side effect or at high doses.

4. Other Cognitive enhancers:
1. Racetams:
– Piracetam
– Oxiracetam
– Phenylpiracetam
– Aniracetam
2. Citicoline
3. Choline bitartrate
4. Alpha GPC
5. Tolcapone

5. 6. Levodopa
7. Atomoxetine
8. Desipramine
9. Nicergoline.
10. Herbs:
– Bacopa monnieri
– Panax ginseng
– Ginkgo biloba
– Salvia officianlis
– Centalla asiatica

6. Caffeine
• 99% bioavailable – can build tolerance → dec. Bioavailability → effects
dependent on individual
• Flow-limited drug: excreted in urine; effects are partly dependent on B.F. to
kidneys
– Exercise: renal blood flow suppressed →half-life extended
• IOC limit: 12ug / mL or less
• Caffeine = methylated xanthine→ metabolized into theophylline and
theobromine
• Theophylline relaxes smooth muscles in airways (found in cocoa beans and tea)
• Theobromine is a vasodilator (inc. muscle and pulmonary BF)- found in dark
chocolate
• Broad effects:
• Stimulates CNS
• Stimulates cardiac tissue

7. • Absorbed in 30-60min → peak levels in about 60 min → half-
life 2-10hr
• Typical doses of 85-250mg
– Coffee = 100 mg of caffeine/6oz serving
– Tea = 60mg/6oz serving (also has Phenylephrine)
– Chocolate = 6mg caffeine + 44mg theobromine /1oz
– Coke/Pepsi = 17mg/6oz serving
– Mountain dew = 27mg/6oz serving
– Volt = 35mg/6oz serving
– Monster = 60mg/6oz serving
– No name = 200mg/6oz serving

8. Caffeine Actions
– Blocks action of adenosine
– Adenosine: stimulates gluconeogenesis, inc. sympatho-
adrenal response to exercise, inc. Myocardial
– glucose uptake during exercise, controls EPO production
by kidneys, critical component of ATP

9. Effects:
– Increased alertness, clearer thinking, shorter reaction time,
increased attention capacity
– Increased epinephrine production → inc. fat oxidation
during ex (more ATP can be made)
– Vasoconstriction
– Bronchodilatation
– Increases TV and dec. respiratory rate
– Dec. NM reaction time in simple tasks (react faster)

10. – Constricts cerebral blood vessels (headache, migraine)
– Increased in body metabolism (lipolysis- controls release of free
fatty acids in blood)
– Increase in CO, HR, BP (SBP and DBP), and body temperature
(largely comes from inc. in metabolism)
– Caffeine increases BP response to exercise (230/>100mmHg
during max exercise)- problem!
– Typical SBP peak is about 200
– Diuretic

11. • Exercise, Caffeine, and the CNS
• Research results have been inconsistent → likely related to specific
subject characteristics
• Caffeine induces an inc. in epi release proportional to dose, but does
not affect running performance
• The effect of caffeine on epinephrine release may be greater in
trained vs. untrained stimulants
• Once exercise begins, changes in epinephrine and Norepinephrine
reflect exercise rather than caffeine

12. Caffeine Effects on Exercise
• Effects on HR depend on the subject characteristics- results are again
inconsistent
• Study- non-habitual caffeine users (less than 1 cup coffee/day)
• One study found no effect on exercise, HR when subjects were dosed at
6mg/kg caffeine
• Open- rest placebo; closed- rest caffeine, open triangles- ex placebo, closed
triangles- ex caffeine
• Changes in MAP are driven by changes in systolic (systolic is affected by
caffeine)
• HR not affected by caffeine, just exercise

13. • Next: ml of blood going into forearm per 100ml of tissue
• Caffeine causing vasoconstriction at rest
• Caffeine acts as diuretic and blood irritant
• During ex- caffeine gets to renal system less- goes to CV system
• Effects of coffee or caffeine capsules on submax running- only
capsule had effect on endurance
• Cycle ergo meter at 80% vo2max to exhaustion. Caffeine boosted
endurance, but there were no differences between dose (maxed out
response at the lowest dose- 5mg/kg

14. CNS Stimulants
• Reduce sleepiness (narcolepsy), increase activity/euphoria
• Can impair dopamine reuptake and activate brain stem/cortex
arousal centers
• Act like sympathomimetic, can be mildly addictive
• Used to treat ADD, ADHD, and narcolepsy
• Side-effects: rapid HR, fever, sore throat, skin rash,
lightheaded, aggression, restlessness, HTN, headache, nausea,
nervousness, insomnia

15. Amphetamines
• CNS stimulant (extreme dependence) → blocks reuptake of
Norepinephrine and dopamine
• Used to treat ADHD and narcolepsy
• Raise BP and HR, increase wakefulness
• Don’t improve muscle or cardiopulmonary function- make you care
less about how uncomfortable it is
• Side-effects: palpitations, tachycardia, seizures, HTN, sudden death

16. Action of Amphetamines
• Mimic actions of catecholamines (Epinephrine,
Norepinephrine, Dopamine)
• At periphery:
– Stimulate the direct release of catecholamines
– Bind to catecholamine receptors
– Inhibit catecholamine reuptake
– Inhibit metabolic breakdown of catecholamines
– All result in an increase in catecholamines

17. At central (brain), stimulate:
– Wakefulness, alertness, elevation of mood
– Make you feel invincible, care less about fatigue/pain
– Decreased sense of fatigue, increase initiative and self-
confidence
– An increase in motor activity, speech activity, and a decreased
appetite
– Stimulate the “pleasure center” of the brain
– Rapidly absorbed, peak at about 1-2 hours (don’t last long)
– Clinical effects appear within a half hour

18. Adverse Effects of Amphetamines
– Restlessness, dizziness, tremor, and insomnia
– More severe- confusion, delirium, paranoia
– Convulsions, coma, and death may follow
– Side-effects from chronic use: compulsive repetitive
behaviour and dyskinesias (lose motor control in face)
– Long term- can cause anorexia (because suppresses
appetite)
– HTN, angina, and cardiac arrhythmias
– Vomiting, abdominal pain, weight loss
– Haemorrhage and seizures (even first-time use)

19. Adverse Reactions of CNS Stimulants
Excessive CNS stimulation, causing:
– Headache
– Dizziness
– Apprehension
– Disorientation
– Hyperactivity
– Nausea and vomiting
– Cough
– Dyspnea
– Urinary retention
– Abnormal heart rate

21. Thank you