Adenosinergic

Caffeine is the world's most widely used psychoactive compound, a methylxanthine that works by blocking adenosine receptors. At low to moderate doses it reliably improves alertness, vigilance, attention and reaction time, with weaker and less consistent effects on memory and higher-order judgment. It is the reference point every other stimulant on this wiki gets compared to.

KW-6356 (sipagladenant) is a selective blocker and inverse agonist of the adenosine A2A receptor, made by Kyowa Kirin, the company behind istradefylline, for Parkinson's disease. In a 12-week trial in 168 people with early, untreated Parkinson's disease, motor scores improved more than on placebo, but the difference was about 2 points and its confidence interval crossed zero; a 503-patient trial as an add-on to levodopa met its primary endpoint, and has been reported only as a conference abstract. Insomnia was the commonest side effect in healthy volunteers. Kyowa Kirin stopped developing it in 2022.

Paraxanthine (1,7-dimethylxanthine) is what most caffeine turns into in the body: about 80% of a caffeine dose is converted to it. Like caffeine it blocks adenosine receptors, and at 4 mg/kg it raised diastolic blood pressure and adrenaline in people about as much as the same dose of caffeine. It is now sold on its own as a supplement. Small crossover trials funded by the ingredient's sponsor report better scores on some attention, memory and reaction-time tests after 50 to 200 mg, though their main statistical tests were not significant.