pharmacology of CNS stimulants and Nootropics

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