Since its discovery as component of the tea leaf by Albert Kossel in 1888, the history of theophylline (CAS 58-55-9) has been a long and successful one. At the turn of the century, theophylline became less expensive due to chemical synthesis and was primarily used as diuretic in subsequent years. It was Samuel Hirsch who discovered the bronchospasmolytic effect of theophylline in 1992, however, despite this pioneering discovery theophylline continued to be used primarily as diuretic and cardiac remedy. The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3 and PDE4, but the anti-inflammatory effect may be due to histone deacetylase (HDAC) activation, resulting in switching off of activated inflammatory genes. Theophylline is indicated for the treatment of acute exacerbations of the symptoms and reversible airflow obstruction associated with asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.

Diphenhydramine is an antihistamine which is used in the combination with naproxen sodium for the relief of occasional sleeplessness when associated with minor aches and pains. Diphenhydramine has a role nighttime sleep-aid and naproxen sodium is a pain reliever. In addition, diphenhydramine used in relieving symptoms in patients with moderate-to-severe seasonal allergic rhinitis. Diphenhydramine acts as an antagonist of histamine H1 receptor. Besides, was shown potential to repurpose diphenhydramine as an anti-melanoma therapeutic agent, it induces melanoma cell apoptosis by suppressing STAT3/MCL-1 survival signaling pathway.

Chlorotheophylline (8-Chlorotheophylline) is a stimulant drug of the xanthine chemical class, with physiological effects similar to caffeine. Its main use is in combination with Diphenhydramine as the antiemetic drug Dimenhydrinate (marketed as Draminate, Dramamine, Detensor and Gravol among others). Dimenhydrinate is primarily used to treat nausea, vomiting, and dizziness caused by motion sickness.The stimulant properties of 8-chlorotheophylline are thought to ward off the drowsiness caused by diphenhydramine's anti-histamine activity in the central nervous system. 8-chlorotheophylline produces a number of effects including nervousness, restlessness, insomnia, headache, and nausea, which are primarily attributed to its ability to block the adenosine receptor. Because adenosine causes a decrease in neuronal firing, blockade of the adenosine receptor causes the reverse effect resulting in excitation.