2. Cognition & cognitive enhancers
For improving cognition
Classification and Mech. of action
In health & disease
Treating –vs- Doping
3. Mental process involved in gaining knowledge and comprehension
THINKING
REMEMBERING JUDGING
KNOWING
In simple terms:
brain process of acquiring and exploiting knowledge
Cognition & cognitive enhancers
5. For improving cognition
Increasing blood flow
Enhancing neurotransmission
Increased neuronal metabolism: stimulation
of hormones and enzymes
Increased nerve growth factor
Improvement of cerebral functions -
memory
6. Neuroscience
Learning Memory
of
&
Explicit memory Implicit memory
Knowledge of facts - what we know
about places, things and people–and
the meaning of these facts
Involves information about how
to perform something, it’s
recalled unconsciously
Long term potentiation
Habituation
Sensitization
8. process
formation
Memoryof
Brain undergoes a physical and chemical
change which is called - Synaptic
Plasticity
lasts for seconds or minutes
lasts for days to weeks
once stored, can be recalled up to
years or even for a lifetime
10. Cellular mechanisms
Neuro-degenerationof
Mis-folded, aggregated proteins
Oxidative stress
Excito-toxicity
α – synuclein → Parkins
Amyloid β and Tau → Alzheimers
Huntingtin – HD
SOD, TDP43 → ALS
Age related decline in ability to
clear misfolded proteins
}
Neuronal injury resulting from excessive glutamate activity in the brain
Destructive effects mediated by NMDA r
MoA – acute stroke and head trauma
Aging – impaired capacity of neurons to handle oxidative stress
ROS – DNA damage, peroxidation of membrane lipids and neuronal death
13. ↑ ACh activity in the brain
↑ glutamate activity via
AMPA and NMDA receptors
~ improve membrane
permeability of neurons →
enhances overall neuronal
function
off-label ADHD
treatment
PIRACETAM
14. 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
effective as an anti-
anxiety and anti-
depression treatment
Aniracetam
15. 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
mental clarity and
concentration
also improving critical
thinking skills
speed of information
processing
Pramiracetam
16. 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 an D3 receptors
& selective Serotonin receptors
↑ Nerve Growth Factor -
maintenance and repair of healthy
brain cells
investigated as a possible
treatment for Alzheimer’s
disease
Age-Related Memory Loss
depression & anxiety
Noopept
17. 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
treat apathy and improve
motivation in post-stroke
patients
Anti-amnesia effects
powerful anxiolytic
successful in the
treatment of clinical
depression
Nefiracetam
19. ACh is an excitatory NT
attention, synaptic plasticity,
wakefulness and the reward
system
↑ cholinergic activity:
improve focus, working
memory, alertness, mental
clarity and performance
1928: Chavany
recovery of cortical function
with cholinergics (hemiplegia)
at first attributed to cerebral
vasodilatation
20. 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 effects
powerful anxiolytic
successful in the treatment
of clinical depression
Choline
21. 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
Alpha - GPC
(Alpha Glycerylphosphorylcholine)
22. 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
citicoline
approved for treatment in cases
of head trauma, stroke
neurodegenerative diseases
25. 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)
26. 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
Sunifiram
alleviate symptoms of
ADHD
28. Smart drugs: interact with natural neurochemicals, such as
hormones, enzymes and neurotransmitters
benefit in cognitive disorders like ADHD, anxiety, Alzheimer’s
and Parkinson’s.
In healthy: substantial boost to normal thinking, learning,
memory, and focus.
considered separately – they may use stimulatory mechanisms
of action and may carry a greater risk of side effects
29. Eugeroic: wakefulness promoting
agent
Stimulates the release histamine in
CNS to promote wakefulness
~ α1-adrenergic receptor agonist
treatment of narcolepsy
ADHD
Shift work sleep disorder
obstructive sleep apnea
potentially useful: depression,
bipolar, opiate and cocaine
dependence, Parkinson's,
schizophrenia and disease-
related fatigue
seasonal affective disorder
Modafinil
30. Modafinil
“Modafinil improves some aspects of working
memory, such as digit span, digit manipulation and
pattern recognition memory, but the results
related to spatial memory, executive function and
attention are equivocal”
Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ
(2003). "Cognitive enhancing effects of modafinil in healthy
volunteers". Psychopharmacology (Berl.) 165 (3): 260–9.
doi:10.1007/s00213-002-1250-8. PMID 12417966.
-
32. Armodafinil
(R)-enantiomer of the racemic
modafinil
Indirect dopamine r agonist:
inhibits reuptake
narcolepsy and shift work sleep
disorder
adjuvant therapy for obstructive
sleep apnea
Schizophrenia (neg sym)
BPAD
Jet lag
33. Methylphenidate
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
ADHD
Off-label: treatment-resistant
lethargy, BPAD, major
depressive disorder
34. any compounds which interact with GABAergic neurons in the
brain
GABA: natural inhibitory effect on stress responses in the
central nervous system
35. Phenibut
derivative of GABA
GABA cannot cross BBB
Phenibut: fully bioavailable
Directly stimulate both GABA-A
and B receptors non-selectively
post-traumatic stress
disorder, anxiety, and
insomnia
(β-phenyl-γ-aminobutyric acid)
37. Regulate metabolism and synthesis of dopamine
are often direct pre-cursors to dopamine
used to treat severe dopamine deficiency disorders like
Parkinson’s disease, schizophrenia, and bipolar disorder
May also be effective treatments against symptoms of ADHD,
anxiety, and depression
38. Sulbutiamine
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
Asthenia: chronic
fatigue of cerebral
origin
improves memory in
schizophrenics and AD
39. Rasagiline
Irreversible inhibitor of monoamine
oxidase →↑Dopamine
neuro-protective and neuro-rescuing
property: effect on the mitochondria
→ interferes with and blocks apoptosis
in neurodegenerative disorders
Monotherapy in Early PD
Adjunct Therapy in
Advanced PD
~ treatment of Restless
Legs Syndrome, AD
40. Rasagiline
Irreversible inhibitor of
monoamine oxidase →↑D
neuro-protective and neuro-
rescuing property: effect on
the mitochondria – interferes
with and blocks apoptosis in
neurodegenerative disorders
Monotherapy in Early PD
Adjunct Therapy in
Advanced PD
~ treatment of Restless
Legs Syndrome, AD
Selegiline
44. Vincamine
Derived from the Vinca Minor
(Periwinkle) plant
↑ blood flow to the brain
improve memory capability in
Alzheimer’s disease
45. Vitamin B1 (Thiamine)
Vitamin B3 (Niacin)
Vitamin B5 (Pantothetic Acid)
Vitamin B6 (Pyrodoxine)
Inositol
Vitamin B12 (Cobalamin)
Low levels: fatigue, depression,
and poor memory
deficiency can potentially cause
severe and irreversible damage to
the brain and nervous system.
48. class of hormones manufactured by neuroendocrine cells
stimulation of cellular growth, stress responses, fight or flight
responses, emotional balancing etc.
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. Pregnenolone
Neurosteroid which is derived from cholesterol
in the adrenal glands, liver, brain, skin, and sex
organs
affects synaptic functioning, neuroprotective,
and enhance myelinization
Improve cognitive and memory functioning
~ Pregnenolone is also being considered as a
potential treatment for schizophrenia
52. In health & disease
Alzheimer's
Dementia (senile/vascular)
TIA, CVA
MR and ADHD in children
Head injury
Schizophrenia
OCD
Phobias
Depression
Exam going students
High stressful jobs which
need complete focus:
neurosurgeons, pilots,
military personnel
Artists
Athletes
53. Treating –vs– Doping
Unfair advantage?
Where to draw the line?
Promotes laziness and shortcuts?
Long term effects?
US army 2012 Afghanistan incident
Trans-humanism?
55. 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.
56. 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.
