nootropics Flashcards
how does risk of dementia change w age
1 in 25 of people aged 70-79, 1 in 6 people over 80
how good is current dementia treatment
used to treat behavioural and cognitive symptoms but has little effect on the underlying pathophysiology, targets cholinergic and serotoninergic systems, but less than 10% of patients respond to such treatment
what was the first nootropic
piracetam, showed to boost memory, learning, creativity, verbal fluency and brain circulation
what are the 5 nootropic principles
a nootropic should enhance learning and memory
should enhance the brains resistance of learned behaviours and memory to conditions that would disrupt them (such as hypoxia or electroconvulsive shock)
a nootropic should protect brain from chemical or physical assaults (such as disruption from scopalamine or barbituates)
should increase the efficacy of the tonic cortical/subcortical control mechanisms
should lack the usual pharmacology of other psychotropic durgs ( they shouldnt impair motor function or possess sedative qualities), very few side effects, low toxicity
what is a plausible mechanism for cognitive enchancers
they strengthen inter-synaptic communication between neurones and brain circuits that are important for learning and memory
how do nootropics relate to ltp
repetitive activation of excitatory synapses results in long lasting increase in synaptic transmission-LTP, underlies forms of learning and memory
both in vitro studies and animal behaviour experiments suggest nootropic drugs facilitate the induction of LTP in hippocampus, leading to synapse reinforcement, which is thought to underlie memory storage and recall, can improve cognitive and memory deficits associated w dementia
associated w lowering the threshold of induction of LTP
what are different classes of nootropics
natural; e.g caffeine
synthetic e.g modafinil, racetams
what classes do piracetam like drugs fall under
cognitive enhancers: piracetam
anti epileptics
drugs w unknown clinical efficacy
what is mode of action for piracetam like cognitive enhancers
activation of AMPA receptor but not kainate or NMDA receptors, their effect is proposed to occur via an increase in the density of receptor binding sites and elevation of intracellular calcium levels
in 1993 croisile and others performed a study which shouwed that long term administration of piracetam could slow deterioration in patients w alzheimers, more evidence as an effective drug in patients w cognitive deterioration or stroke induced short term memory
can reduce cognition loss mediated by scopolamine perhaps via the purinergic system causing a decrease in oxadative stress and a corresponding maintenance of NTPDase and ADA levels in synaptosomes in cerebral cortex and hippocampus
what may piracetam treat
no significant improvement in AD
can be used in polytherapy with vasodilator cinnarizine to treat multiple sclerosis, showed improvements in activity and mood
may also be used in combination therapy in patients with the antipsychotic risperidone, results showed improvements in abnormal behaviour in patients w autistic disorders
what is piracetams pharmacology
weak positive modulator of AMPA receptors, binds to S1S2 dimer interface of GluA2
describe the antiepileptic family of piracetam like drugs
includes seletracetam
mechanism; inhibition of neuronal calcium ion channels
what is modafinil
FDA approved eugeroic (promotes wakefulness) to treat narcolepsy and other sleep disorders
used as an off label cognitive enhancer
what is modafinils mechanism
produces an overall excitatory effect
proposed mechanism; increasing conc of glutamate and decreasing GABA within posterior hypothalamus
improves digit span, visual recognition memory, spatial planning
multiple effects on different brain areas and NTs
activates different circuits and brain areas compared to amphetamine and methylphenidate, while sharing inhibition of dopamine reuptake as mechanism underlying its pharmacological effects
may produce cognitive improvement in a number of neurological and psychiatric disorders with low abuse liability
how may modafinil be used in polytherapy
may be used as an adjunct to antipsychotics in order to ameliorate cognitive impairments in schizo
what are factors of nootropic clinical trials
design of trial has to consider two elements:
the probability of acheiving desired change in patients cognitive function: one mehcanism is counteracting the damage caused by mental decline; can only be observed when mental decline equates to mild intellectual deterioration, early signs of dementia are often good experimental subjects, elderly patients w dementia, depression and variation in cognition arousal can be improved indirectly via improvement of patients mood and motivation making them poor subjects
the interpretation or acheivement of an observed change in the requisite cognitive task; has to be measured in a neutral environment; factors that can improve or reduce cognitive performances have to be excluded
what are side effects of nootropics
armodafinils adverse effects include headache, diarrhea and nasopharyngitis
piracetams users reported symptoms of psychomotor agitation, dysphoria, tiredness, dizziness, headache and diarrhea
what is clausenamide
possesses nootropic activity and enhances LTP
comes in racemic +/- form
(-) clausenamide potentiates basic synaptic transmission, potentiates high frequency stimulation induced LTP
- form is 5-10 times more active than racemic mixture, and 50-100 times more active than piracetam
what is the clausenamide challenge
10 kilograms of dried leaves produces on 3.8g of clausenamide, possible synthetic approach
what is BRS015
facilitates synaptic transmission, displayes 1000 fold greater activity when compared to piracetam in identical assays
selectively potentiates AMPA/ kainate receptor mediated EPSCs but has no effect on both NMDA and kainate EPSCs
enhances glutamate evoked currents in CA3 pyramidal neurones
CC50 (cytotoxic) was found to be over 800uM, has an EC50 of 12uM
