Methylxanthines and Nootropics Flashcards
1
Q
Caffeine
A
- methylxanthine
- most consumed behaviourally active substance
- similar but milder effects as classic psychostimulants (motor activation, arousal, concentration, wakefulness)
- seems to potentiate dopamine system
2
Q
Guaranine or Metaeine
A
- “organic alternative to caffeine”
- chemically identical to caffeine but comes from different sources (yerba mate and guarana plants)
3
Q
General Physiological Effects
A
- increase release of NTs 9including adrenaline)
- activation of cortex
- dilation of blood vessels in periphery but constriction of cranial vessels (has complicated bp effect, forces oppose each other)
- relaxation of smooth muscle, stimulation of skeletal muscle
- diuretic (300+ mg), increase blood flow to kidneys, weakens bladder, inhibits resorption of water and sodium
4
Q
Is it a cognitive enhancer?
A
- depends on test whether inhibits or enhances learning and memory
- increases if tired or bored (help stay awake and concentrate) but doesn’t improve beyond level of rested brain doing not bring task
5
Q
What is adenosine? What effect does caffeine have to adenosines effects?
A
- neuromodulator
- decreases release of NTs (calming effect)
- presynaptically prevents NTs release and postsynaptically depressant effects
- caffeine prevents all of these effects by binding to receptor (blocks calming effect leads to stimulant effect)
6
Q
What does caffeine do?
A
- antagonist at adenosine receptors
- A1 and A2A seem to be most important for caffeine effects (most effects due to A1 likely, A2A involved in process of keeping you awake)
7
Q
A1 vs A2A receptors
A
A1: presynaptic, inhibits cAMP, inhibits NT release, distributed thoughout brain
A2A: both pre and post synaptic, stimulates cAMP productions, promotes NT release (GABA), mostly in NAcs
8
Q
Effects on sleep
A
- if drink caffeine at night pushes back sleep wake cycle 45 minutes
- adenosine levels climb during waking until point this is reached that triggers sleep
- adenosine binding to A2A receptors in the hypothalamus trigger GABA release (inhibits arousal system)
- caffeine prevents adenosine from binding to A2A receptors, prevents GABA release, inhibit sleep
9
Q
At higher doses what else does caffeine target?
A
- inhibits phosphodiesterase (PDE) enzymes which metabolize cAMP (get increased cAMP)
- > results in relaxation of smooth muscle (vasodilation) and increase contraction of heart muscles
- inhibits GABA-A receptors (seizures)
- increases calcium channel function (more Ca2+ in cell so more likelihood of NT release)
- > increase work capacity of muscle
10
Q
Which is the most important target?
A
(dose and effect graph in notes)
- A1 and A2A primary target (at normal levels of caffeine probably only these)
- some suggest PDE as well
- other effects like (PDE, Ca2+, and GABA-A) only at toxic dose generally (unlikely to take this much
11
Q
Metabolism of Caffeine
A
- liver
- 3 primary metabolic products:
1) paraxanthine (increases lipolysis, leads to elevated glycerol and free fatty acids in blood plasma)
2) theobromine (dilates blood vessels and increases urine volume)
3) theophylline (relaxes airway smooth muscle)
12
Q
Is it a drug of abuse?
A
- robust dopamine increase in the nucleus accumbens
- seems due to block of A1 receptors that normally inhibit dopamine and glutamate release (so get increase DA and Glu (which further increases DA levels))
13
Q
Caffeinism
A
- preoccupation with and overuse
- agitation, anxiety, muscle twith, heart palpitations, increased temperature
- abrupt termination leads to symptoms
14
Q
How much caffeine is lethal?
A
10 g (100 cups of coffee) -death from convulsion, respiratory arrest
15
Q
Health risks
A
- seizures in young people
- osteoporosis (neg effects on bone density)
- > increases urinary excretion of calcium and inhibits absorption from diet
- increased risk of panick attacks (mostly in those with specific mutation in A2A receptor)
