Post on 20-Feb-2017
CAFFEINE & YOU
CAFFEINE & YOU
david ardiansyah & koh jia lei
Caffeine noun caf·feine \ka-ˈfēn, ˈka-ˌ\German Kaffein, from Kaffee coffee, from French café
Caffeine noun caf·feine \ka-ˈfēn, ˈka-ˌ\German Kaffein, from Kaffee coffee, from French café
the world consumes 2 billion cups of coffee daily!
a sharpened focus
extra boost of energy
warding off drowsiness
sleep disorders
anxiety
addiction and withdrawal syndrome
PROLONGEDconsumptions
STIMULANTS
STRUCTURE
odourless
tastes bitter
white powder
CAFFEINE
purine ring
two ketone
purine xanthine
1,3,7-trimethylxanthine
CAFFEINE
causes drowsiness
dilation of blood vessels (vasodilation)
slowing down cerebral cell activity
ADENOSINE
purine ring
ribose ring
(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
ADENOSINE
caffeine
amine
adenosine tri-phospate (ATP)
adeninebuilding blocks of DNA (‘A’ ’T’ ‘C’ ‘G’)
energy storage for biochemical process
adenosine
induces sleep
Adenosine docking at Adenosine A2a receptor
π bond interaction
RESONANCE
Glu169A
Asn253A
His278A
resonance effect strengthens the hydrogen bonds
glutamic acid
asparagine
histidine
MECHANISM OF ACTION
CROSSING BLOOD-BRAIN BARRIER
highly lipophilic
Caffeine has a value of approx. -0.25 to -0.55
Partition-coefficient (P)
To cross the blood-brain barrier, the log P value is < 3
Passive diffusion of caffeine
Ride on Adenosine transport mechanism
Caffeine docking at Adenosine A2a receptor
π bond interaction
CaffeineAdenosine
π bond interaction π bond interaction
METABOLISM OF CAFFEINE
Caffeine
Paraxanthine 84%
Theobromine 12%
Theophylline 4%
increases the rate of lipolysis process
Paraxanthine
dilation in the blood vessels
increases urine production
Theobromine
induces bronchodilation
Theophylline
increased heart rate and contractility
caffeine crash
caffeine resistance
caffeine withdrawal symptoms
up regulation of receptors increased number of receptor active sites
more adenosine can bind into extra receptor actives site higher sensitivity of adenosine in the brain
caffeine unbinding once being metabolised adenosine readily binds to active side
AFTER EFFECT
ADENOSINE RECEPTORS
four different subtypes: A1, A2a, A2b and A3
purinergic receptors
ADENOSINE RECEPTORS
decrease the amount of cAMP (cyclic Adenosine Mono-Phosphate)
inhibiting enzyme Adenylate Cyclase
A1 and A2a play a complementary role
ADENOSINE A2a RECEPTOR AGONISTS
ligand that binds into a receptor and begins to activate the receptor
strict requirements
esp. structure and stereochemistry of the ribose group
1
2
3 tolerated modifications are shown at (1), (2) and (3).
adenosine A2a receptor agonists
5’-hydroxyl group of the ribose ring, 2- and N-6 position of the purine group
Ki value for Adenosine A2a Agonists
NECA and Adenosine docking at Adenosine A2a Agonists
ADENOSINE A2a RECEPTOR ANTAGONISTS
ligand that binds to a receptors and causes the blocking of the agonist-mediated response
a planar configuration, aromatic or π electron rich and nitrogen containing heterocycle
lack of ribose group
N1, N3, N7 and C8
xanthine antagonists at adenosine A2a receptor
modification at N1, N3, N7 and C8
non-xanthine antagonists at adenosine A2a receptor
Ki value for Adenosine A2a Antagonists
Ki value for Caffeine is 4,5000, 18,000 and 13,000 at A1, A2a and A3 respectively
Caffeine and XAC docking at Adenosine A2a Agonists
ADENOSINE A2a RECEPTOR PARTIAL AGONISTS
less than half the intrinsic activity
a combination of an antagonistic substituent of purine ring and the unchanged agonistic ribose group
modifications on the purine group
Theophylline-7-riboside 1,3-dibutylxanthine-7-riboside
FURTHER APPLICATION
ANALGESICS
synergistic effect with paracetamol
caffeine on its own has no analgesic effects
adenosine often detected in migraine attacks
competitive inhibition of the adenosine receptors
PARKINSONS
caffeine may have beneficial effect in treatment of Parkinson
up-regulation of adenosine receptors changes adenosine-dopamine proportions
dopamine pathway would be stimulated
theophylline may also achieve similar effect
dopamine pathway has similar mechanism of action to that of Anti-Parkinsonian drugs induces
PARKINSONS
adenosine A2a receptor is found co-localised with the Dopamine D2 receptor
dopamine receptors are known to be obligatory synergistic
adenosine-receptor binding decreases the affinity of the D2 receptors agonists
MÉRCI
KOPITALK