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