Adenosine antagonists

Caffeine and theophylline affect cerebral circulation, most likely through their effect as adenosine antagonists. 

Most likely the major action of methylxanthines as adenosine antagonist is the reason for these effects on the renal system. 

The main mechanism of action of caffeine occurs via the blockade of adenosine receptors in the CNS. Adenosine is an autacoid, which is involved in the modulation of behavior, oxygenation of cells, and dilatation of cerebral and coronary blood vessels and indirectly inhibits the release of dopamine. The blockade of adenosine receptors by caffeine increases the activity of dopamine, which is implicated in the effects of caffeine (91). The question that arises from this observation is to know whether or not adenosine antagonists hold potential for the treatment of Parkinsonism, and further study on the adenosine receptor antagonists from medicinal plants should be encouraged. A possible source for such agents could be the medicinal flora of Asia and the Pacific, among which is the family Sapindaceae. 

Coffee Coffea sp. Caffeine Adenosine (antagonist) Adenosine... 

Bronchodilation is promoted by cAMP. Intracellular levels of cAMP can be increased by 13-adrenoceptor agonists, which increase the rate of its synthesis by adenylyl cyclase (AC) or by phosphodiesterase (PDE) inhibitors such as theophylline, which slow the rate of its degradation. Bronchoconstriction can be inhibited by muscarinic antagonists and possibly by adenosine antagonists. 

Akahane, A. et al.(Fujisawa Pharmaceutical Corporation, Ltd) Pyrazoiopyrazines and their use as adenosine antagonists, WO 0140230, Pyrazoiopyrazines as adenosine antagonists, WO 0024742. 

Theophylline may also act as an adenosine antagonist.86 113 Adenosine is thought to bind to specific receptors on the smooth-muscle cells and to stimulate contraction. By blocking this effect, theophylline would facilitate smooth-muscle relaxation. Theophylline may likewise help produce bronchodilation by other mechanisms, such as inhibition of intracellular calcium release and stimulation of catecholamine release.115 In reality, theophylline and similar drugs may induce bronchodilation and help protect the airways through a combination of several mechanisms, but the relative importance of each cellular effect remains to be determined. 

Another proposed mechanism is the inhibition of cell surface receptors for adenosine. These receptors modulate adenylyl cyclase activity, and adenosine has been shown to cause contraction of isolated airway smooth muscle and to provoke histamine release from airway mast cells. These effects are antagonized by theophylline, which blocks cell surface adenosine receptors. It has also been shown, however, that xanthine derivatives devoid of adenosine-antagonistic properties (eg, enprofylline) may be more potent than theophylline in inhibiting bronchoconstriction in asthmatic subjects. 

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