Mechanism of action (MOA) of Caffeine

Question

Most people get a temporary increase in wakefulness or better ability to concentrate after caffeine intake.

There are several known mechanisms of action to explain the effects of caffeine. The most prominent is that it reversibly blocks the action of adenosine on its receptor and consequently prevents the onset of drowsiness induced by adenosine. Caffeine also stimulates certain portions of the autonomic nervous system.
Source: Wikipedia

How does caffeine block the adenosine receptors? How does it stimulate the autonomic nervous system?

Answer 1

Caffeine is an antagonist at adenosine receptors 1 and 2A. This means it binds to said receptors without activating them. The presence of caffeine at the adenosine receptors prevents adenosine (an inhibitory neurotransmitter) from binding (and producing a response), thereby causing stimulation (1) . This activity also induces neurotransmitter release (2) .

Caffeine is structurally similar to adenosine. (3) This underlies it ability to bind to the same receptors.

Figure 1 Comparison of the structural formulas of caffeine and adenosine (4)

The autonomic effects of caffeine are also mediated through caffeine's activity at the adenosine receptors (2).

References

1. http://lpi.oregonstate.edu/mic/food-beverages/coffee
2. https://web.archive.org/web/20170208153409/https://www.drugbank.ca/drugs/DB00201
3. https://www.researchgate.net/publication/8608761_Caffeine_as_a_psychomotor_stimulant_Mechanism_of_action
4. https://www.sciencelearn.org.nz/images/2456-caffeine-and-adenosine-structure