Gisadenafil is a phosphodiesterase V inhibitor in clinical development at Pfizer. It had been in phase II clinical trials for the treatment of Benign prostatic hyperplasia; Chronic obstructive pulmonary disease; Erectile dysfunction; Overactive bladder. Treatment-emergent adverse events were: headache, myalgia, dyspepsia, back pain.

PH-797804 is a diarylpyridinone inhibitor of p38alpha mitogen-activated protein. The drug was developed by Pfizer for the treatment of inflammatory diseases. PH-797804 is being tested in phase II of clinical trials in patients with COPD, osteoarthritis, rheumatoid arthritis and post-herpetic neuralgia.

CVT-6883 (GS 6201) is an A2B adenosine receptor antagonist originated by CV Therapeutics and developed by Gilead Sciences or the treatment of pulmonary diseases. In vitro studies have suggested that the activation of the A2B adenosine receptor may potentially have Proinflammatory and profibrotic effects that could be significant in the development of lung diseases. In adenosine deaminase (ADA) deficient mice, treatment with GS 6201 resulted in significantly less pulmonary inflammation, fibrosis, and alveolar airway enlargement compared with ADA-deficient mice treated with placebo. A range of doses of GS 6201 was well tolerated in healthy volunteers in a phase I multiple ascending dose trial.

GW-311616, a specific NE inhibitor, may act as a potential targeted drug for leukemia, which may have a profound impact on the future of leukemia-targeted therapy. GW-311616 hydrochloride is a potent, selective, intracellular, orally bioavailable and long duration inhibitor of human neutrophil elastase (HNE) with an IC50 value of 22nM. GW-311616 hydrochloride has been found to be selevtive over other human serine proteases with IC50 values of 22nM for HNE, >100uM for trypsin, cathepsin G, and plasmin, >3uM for chymotrypsin and tissue plasminogen activator. In HNE enzyme kinetic tests, GW-311616 has been reported to inhibit HNE with a Ki value of 0.13nM. In addition, GW-311616 has been revealed to inhibit HWB with an IC50 values of 0.67uM in HWB assay. Moreover, by measurement of intraneutrophil elastase activity, GW-311616 hydrochloride has been suggested to have a dose-response and duration of action in blood samples of dog. At present, although research on GW-311616 has being dropped at the preclinical stage, the beneficial profile of oral GW-311616 may make it usuful in the design of new drugs.

Imperialine is a steroidal alkaloid first isolated from the bulb of Fritillaria imperialis L. (Liliaceae). Bulbs of Fritillaria have been used in many Asian countries for a long time to treat pulmonary diseases, such as cough, expectoration, and asthma. Imperialine is one of the biologically active constituents in Fritillaria. It acts as a selective antagonist at muscarinic M2 receptors. It exerts antitussive, expectorant, and anti-inflammatory properties. In addition, imperialine demonstrated antineoplastic potential in vitro.

Bitolterol is a beta 2-adrenergic agonist. Since it in itself is biologically inactive, bitolterol is considered a pro-drug. When administered it is activated within the lung by esterase hydrolysis to the active compound colterol catecholamine N-t-butyl-arterenol. Bitolterol was marked under the name tornalate and was indicated to prevent and treat of reversible bronchospasm associated with asthma or chronic obstructive pulmonary diseases. But that drug was withdrawn from the market by Elan Pharmaceuticals in 2001.

Quercetin is a unique bioflavonoid that has been extensively studied by researchers over the past 30 years. Quercetin, the most abundant of the flavonoids (the name comes from the Latin –quercetum, meaning oak forest, quercus oak) consists of 3 rings and 5 hydroxyl groups. Quercetin is a member of the class of flavonoids called flavonoles and forms the backbone for many other flavonoids including the citrus flavonoids like rutin, hesperidins, Naringenin and tangeritin. It is widely distributed in the plant kingdom in rinds and barks. The best described property of Quercetin is its ability to act as antioxidant. Quercetin seems to be the most powerful flavonoids for protecting the body against reactive oxygen species, produced during the normal oxygen metabolism or are induced by exogenous damage [9, 10]. One of the most important mechanisms and the sequence of events by which free radicals interfere with the cellular functions seem to be the lipid peroxidation leading eventually the cell death. To protect this cellular death to happen from reactive oxygen species, living organisms have developed antioxidant line of defense systems [11]. These include enzymatic and non-enzymatic antioxidants that keep in check ROS/RNS level and repair oxidative cellular damage. The major enzymes, constituting the first line of defence, directly involved in the neutralization of ROS/RNS are: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) The second line of defence is represented by radical scavenging antioxidants such as vitamin C, vitamin A and plant phytochemicals including quercetin that inhibit the oxidation chain initiation and prevent chain propagation. This may also include the termination of a chain by the reaction of two radicals. The repair and de novo enzymes act as the third line of defence by repairing damage and reconstituting membranes. These include lipases, proteases, DNA repair enzymes and transferases. Quercetin is a specific quinone reductase 2 (QR2) inhibitor, an enzyme (along with the human QR1 homolog) which catalyzes metabolism of toxic quinolines. Inhibition of QR2 in plasmodium may potentially cause lethal oxidative stress. The inhibition of antioxidant activity in plasmodium may contribute to killing the malaria causing parasites.

Methoxyphenamine also known as 2-methoxy-N-methylamphetamine (OMMA), is a beta adrenergic receptor agonist nd is used as a bronchodilator to treat asthma, chronic obstructive pulmonary disease (COPD) and postinfectious cough. In addition, methoxyphenamine using is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA).

Fisetin, a natural flavonoid found in various fruits, vegetables, and nuts, has various biological properties, including anti-inflammatory, anti-oxidant, neuroprotective in cell culture and in animal models relevant to human diseases. Fisetin can be also a promising agent for the treatment of uveal melanoma. Besides, it is a therapeutic agent for respiratory inflammatory diseases such as chronic obstructive pulmonary disease (COPD), where fisetin inhibits the TNF-α-activated IKK/NF-κB cascade by targeting PKCδ. In vitro and in vivo experiments have revealed that fisetin possesses significant therapeutic effects against diabetic complications and atherosclerosis, where it can suppress vascular inflammatory processes.

Clenbuterol is agonist of beta2 adrenergic receptor. In some countries it is used as bronchodilator for treatment of asthma, but is not approved in USA. The drug is abused by bodybuilders and athletes for its ability to increase lean muscle mass and to reduce body fat. In 1998 FDA approved the clenbuterol-based Ventipulmin Syrup as a prescription-only drug for treatment of airway obstruction in horses.