Several theories have been proposed. At high concentrations, caffeine interferes with the uptake and storage of calcium by sarcoplasmic reticulum of striated muscle. While this action would explain the effects of caffeine on cardiac and skeletal muscle, it does not appear to occur at clinically achievable concentrations. Currently, it is believed that xanthines act as adenosine-receptor antagonists. Adenosine acts as an autocoid, and virtually every cell contains adenosine receptors within the plasma membrane.
Adenosine exerts complex actions.
It inhibits the release of neurotransmitters from presynaptic sites but works in concert with norepinephrine or angiotensin to augment their actions. Antagonism of adenosine receptors by caffeine would appear to promote neurotransmitter release, thus explaining the stimulatory effects of caffeine. Recently, a distinct syndrome has been associated with caffeine withdrawal. It is possible that the manifestations of caffeine withdrawal may be secondary to catecholamine or neurotransmitter depletion. Absorption from suppositories may be slow and erratic.