Nootropics and smart drugs are natural or synthetic substances that can be taken to improve mental performance in healthy people. They have gained popularity in today’s highly competitive society and are most often used to boost memory, focus, creativity, intelligence and motivation. Here’s a look at the ]best nootropics and how they enhance performance.

1. Amr Hassan MD,FEBN
Professor of Neurology - Cairo University
Brain Stimulants

4. A Ch

6. 6
Neurobiology of sleep

7. 7
Hypothalamic and brainstem sleep-wake regulation
system

8. 8
Arousal pathways maintaining cortical activation in the
waking state

9. Neurobiology of sleep

10. SCOPE OF COGNITIVE ENHANCERS IN
HEALTH & DISEASE
Exam going students
stressful jobs which need
complete focus:
physicians, pilots, military
personnel Artists
Athletes
Alzheimer's
Dementia (senile/vascular)
TIA, CVA
MR and ADHD in children
Head injury
Schizophrenia
OCD
Phobias
Depression

15. RACETAMS
• Piracetam
• Aniracetam
• Oxiracetam
• Pramiracetam
• Phenylpiracet
• Nefiracetam
• Coluracetam

16. PIRACETAM
• ↑ ACh activity in the brain
• ↑ glutamate activity via
AMPA and NMDA receptors
• Improve membrane
permeability of neurons →
enhances overall neuronal
function
MECHANISM OF ACTION USE
• off-label ADHD
treatment

17. Aniracetam
MECHANISM OF ACTION
• derivative of Piracetam
• 5x more potent
• also stimulates AMPA receptor: learning
& memory encoding processes
• activate D2 and D3 Dopamine receptors
& 5-HT(2a) receptor involved in
Serotonin processing
USE
• effective as an
anti- anxiety and
anti- depression
treatment

18. Pramiracetam
MECHAAISM OF ACTION
• Piracetam analogue (30x)
• influences both Glutamate and
ACh receptors
• ↑ reuptake at ACh receptor sites as
well as increasing the efficiency of
nerve impulse channels in the
hippocampus → central role in
memory formation as well as recall
USE
• mental clarity and
concentration
• speed of information
processing

19. Noopept
MECHANISM OF ACTION
• Not racetam, but similar MoA
• 1000 X
• high affinity for ACh, AMPA and
NDMA receptors: relate to short-
term and long-term memory
• also activates D2 and D3 receptors
& selective Serotonin receptors
• ↑ Nerve Growth Factor -
maintenance and repair of healthy
brain cells
USE
• investigated as a possible
treatment for Alzheimer’s
disease, Age-Related
Memory Loss
• Depression & anxiety

20. Nefiracetam
MECHANISM OF ACTION
• Potentiates excitatory
neurotransmission → prolonging
the opening of calcium channels
• binds to N-ACh r: ↑ communication
in GABAergc, Cholinergic,
monoaminergic and glutamatergic
neuronal systems
• highly cytoprotective
USE
• treat apathy and improve
motivation in post-stroke
patients
• Anti-amnesia effects
• powerful anxiolytic

21. CHOLINERGICS
Choline
Alpha-GPC
Citicoline
Centrophenoxine
Choline
citrate/bitartarate
DMAE
Lecithin
Phosphatidylcholine
AChE inhibitors
Galantamine
Huperzine A

22. GENERAL PRINCIPLES
• ACh is an excitatory NT
• ↑ attention, synaptic plasticity, wakefulness and the reward
system
• ↑ cholinergic activity: improve focus, working memory, alertness,
mental clarity and performance

23. Choline
MECHANISM OF ACTION USE
• water-soluble essential
nutrient
• structural integrity and
signaling roles for cell
membranes
• ↑ cholinergic
neurotransmission (ACh
synthesis)
• treat apathy and improve
motivation in post-stroke
patients
• Anti-amnesia
• anxiolytic
• Anti depression

24. Alpha - GPC
(Alpha Glycerylphosphorylcholine)
MECHANISM OF ACTION
• occurs naturally in the brain, human
breast milk (associated with ↑IQ in
breast fed babies)
• highest bio-availability of Choline
• readily crosses the blood-brain barrier

25. Citicoline
MECHANISM OF ACTION
• intermediary in the conversion of
choline into phosphatidylcholine in
the liver
• ↑ availability of choline in the
brain by freeing up quantities of
choline
• preservation of cardiolipin and
sphingomyelin
• Citicoline decreases phospholipase
stimulation → less hydroxyl radicals
USE
• approved for treatment in
cases of head trauma,
stroke, neurodegenerative
diseases

26. Centrally acting anticholinesterases
tacrine approvedforthetreatment ofAlzheimer's disease
galantamine mildtomoderatevasculardementiaandAlzheimer's
rivastigmine mildtomoderatedementiaoftheAlzheimer’stype
anddementiaduetoParkinson'sdisease
donepezil approvedforthetreatmentofAlzheimer'sdisease
HuperzineA

27. AMPA-KINES
• Sunifiram
• Unifiram
• Ampalex (CX-516)

28. AMPA-KINES
GENERAL PRINCIPLES
• activate glutamatergic AMPA r:
promote alertness, ↑ attention
span and memory
• ↑ synaptic communication:
promote growth of neurons and
the formation of long term
memories
• potential treatment:
Alzheimer's disease,
Parkinson's disease,
schizophrenia,
treatment-resistant
depression, neurological
disorders such as
Attention Deficit
Hyperactivity Disorder
(ADHD)

29. Sunifiram
MECHANISM OF ACTION
• Sunifiram activates AMPA- mediated
neurotransmission
• It enhances LTP
• improves cognitive deficits via CaM
kinase II and protein kinase C activation
• ↑ release of ACh in the cerebral
cortex
USE
• alleviate symptoms
of ADHD

30. SMART DRUGS
• Adarafinil
• Modafinil
• Armodafinil
• Methylphenidate

31. 31
Eurogenics

32. 32
Armodafinil FDA approval
1. Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS)
2. Narcolepsy
3. Shift Work Sleep Disorder (SWSD)

33. How Armodafinil and Modafinil Are Similar
33
Structurally, two enantiomers make up modafinil: the R-enantiomer and the S-enantiomer
The two compounds are flip-copies of each other, just like your right hand and your left.
Armodafinil consists of only the R-enantiomer of modafinil (in medical jargon, it’s an
enantiopure version of it).
It turned out the R-enantiomer gives much stronger psychoactive effects.
This discovery is ultimately what drove scientists to isolate and produce it as a stand-alone
drug.
.((Claus J. Loland, et al. R-Modafinil (Armodafinil): A Unique Dopamine Uptake Inhibitor and Potential Medication for Psychostimulant Abuse. Biol Psychiatry. (2012) Sep 1; 72(5): 405–413.))
.((Wisor JP, et al. Armodafinil, the R-enantiomer of modafinil: wake-promoting effects and pharmacokinetic profile in the rat. Pharmacol Biochem Behav. (2006) Nov;85(3):492-9.))

34. 34
Modafinil/Armodafinil mechanism of action

35. Methylphenidate
MECHANISM OF ACTION
• Prevents re-uptake of
dopamine & NE
• Also a 5HT1A receptor agonist
• Enhances the function of
neurons in the prefrontal
cortex: impulse control,
motivation, and mental clarity
USE
• ADHD
• Off-label: treatment-
resistant lethargy,
BPAD, major
depressive disorder

36. DOPAMINERGICS
• L-Dopa
• Theanine
• Suntheanine
• Piribedil
• Sulbutiamine
• Rasagiline
• Selegiline

37. DOPAMINERGICS
MECHANISM OF ACTION
• Regulate metabolism and synthesis of dopamine
• are often direct pre-cursors to dopamine
• used to treat severe dopamine deficiency disorders like Parkinson’s
disease
• May also be effective treatments against symptoms of ADHD,
anxiety, and depression

38. Piribedil
MECHANISM OF ACTION
• piperazine derivative which acts
as a D2 and D3 receptor agonist.
It also has α2-adrenergic
antagonist properties
USE
• PD

39. Sulbutiamine
MECHANISM OF ACTION
• Synthetic derivative of thiamine
• Crosses BBB > thiamine
• increases the levels of thiamine and
thiamine phosphate esters in the brain
• improves memory: potentiation of
cholinergic, dopaminergic, and
glutamatergic transmission
USE
• Asthenia: chronic
fatigue of cerebral
origin
• improves memory in
schizophrenics and AD

40. Rasagiline
MECHANISM OF ACTION
• Irreversible inhibitor of
monoamine oxidase
→↑Dopamine
• neuro-protective and neuro-
rescuing property: effect on
the mitochondria → interferes
with and blocks apoptosis in
neurodegenerative disorders
USE
• Monotherapy in Early
PD
• Adjunct Therapy in
Advanced PD
• treatment of Restless
Legs Syndrome, AD

41. COGNITIVE METABOLIC ENHANCER
• Acetyl L-Carnitine
• Alpha Lipoic Acid
• Creatine
• Pyritinol
• Vincamine
• Vinpocetine

42. Acetyl L-Carnitine
MECHANISM OF ACTION
• Crosses BBB
• Converted into Acetyl-COA, which binds with choline
= acetylcholine

43. Vincamine
MECHANISM OF ACTION
• Derived from the Vinca Minor
• (Periwinkle) plant
• ↑ blood flow to the brain
• improve memory capability in
Alzheimer’s disease

44. NATURAL NOOTROPIC
Artichoke Extract
Ashwagandha
Bacopa Monnieri
Forskolin
Grape Seed Extract
Ginseng
Hordenine
Kava Kava
Kratom
Pterostilbene
Rhodiola Rosea
St John’s Wort

46. GINKOBILOBA

47. NEURORMONES
• DHEA (Dehydroepiandrosterone)
• Vasopressin
• Desmopressin
• Melatonin
• Pregnenolone

48. NEURORMONES
• class of hormones manufactured by neuroendocrine
cells
• stimulation of cellular growth, stress responses, fight or
flight responses, emotional balancing etc.

49. DHEA (Dehydro-epiandrosterone)
• neurohormone produced in
human adrenal glands
• commonly used by athletes
as a performance enhancer
• reduce the visible signs of
aging, and prevents neuronal
dysfunction

50. Vasopressin
• exerts several nootropic benefits:
• better short term memory
• heightened metal acuity
• deeper memory imprinting
• used as a treatment for memory issues
relating to age, dementia or
Alzheimer’s disease
• popular with students

51. SCOPE OF COGNITIVE ENHANCERS IN
HEALTH & DISEASE
Exam going students
stressful jobs which need
complete focus:
physicians, pilots, military
personnel Artists
Athletes
Alzheimer's
Dementia (senile/vascular)
TIA, CVA
MR and ADHD in children
Head injury
Schizophrenia
OCD
Phobias
Depression

52. References
Ingole, S. R., Rajput, S. K., & Sharma, S. S. (2008). Cognition enhancers: Current strategies
and future perspectives. CRIPS, 9(3), 42-48.
Bostrom, N., & Sandberg, A. (2009). Cognitive enhancement: methods, ethics, regulatory
challenges. Science and Engineering Ethics, 15(3), 311-341.
Lippincott., Cognitive Enhancers and Neuroprotectants. ln: Gualtieri,T., Brain Injury & Mental
Retardation: Neuropsychiatry & psychopharmacology, 2004; 2nd ed. NY. Wolters Kluer. P: 1-37
Insel T.,Krystal J., Ehlers M. (2013a). New drug development for cognitive enhancement in
mental health: challenges and opportunities. Neuropharmacology 64 2–7
Greely, H., Sahakian, B., Harris, J., Kessler, R. C., Gazzaniga, M., Campbell, P.,& Farah, M. J.
(2008). Towards responsible use of cognitive-enhancing drugs by the
healthy. Nature, 456(7223), P: 702-705.

53. References
www.nootriment.com [last accessed on 25.02.2015]
Swerdlow, N. R. (2012). Beyond antipsychotics: pharmacologically-augmented cognitive
therapies (PACTs) for Schizophrenia Neuropsychopharmacology, 37(1), P: 310.
Lanni, C., Lenzken, S. C., Pascale, A., Del Vecchio, I., Racchi, M., Pistoia, F., & Govoni, S. (2008).
Cognition enhancers between treating and doping the mind. Pharmacological
Research, 57(3), P: 196-213.
Ressler, K. J., Rothbaum, B. O., Tannenbaum, L., Anderson, P.,Graap, K., Zimand, E & Davis, M.
(2004). Cognitive enhancers as adjuncts to psychotherapy: Use of D-cycloserine in phobic
individuals to facilitate extinctionof fear. Archives of general psychiatry, 61(11), P: 1136-1144.
Stip, E., Chouinard, S., & Boulay, L. J. (2005). On the trail of a cognitive enhancer for the
treatment of schizophrenia. Progress in Neuro-Psychopharmacology and Biological
Psychiatry, 29(2), P: 219-232.

54. THANK YOU
amrhasanneuro@kasralainy.edu.eg