Cistinexine is an expectorant drug developed by Italian company Recordati S.p.A. Cistinexine as a cystine derivative that has shown an expectorant action similar to bromhexine during preclinical pharmacological trials. In clinical trials in patients with chronic bronchitis, treatment with cistinexine did not lead to a reduction of mucus transport rate (MTR). The only significant effect was observed in patients with severe impairment of MTR.

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.

Piragliatin is a nonessential, mixed-type (i.e. increases maximal velocity and affinity of glucokinase for glucose) small-molecule activators of glucokinase. Preclinical pharmacology studies confirmed that piragliatin had activity in both pancreatic beta-cell and hepatic cell glucose metabolism. Piragliatin augmented glucose-stimulated insulin secretion (GSIS) in human islets from both normal individuals and patients with type 2 diabetes, primarily by left-shifting the glucose dependency curve of GSIS. In healthy volunteers a single administration of piragliatin showed dose-dependent reduction of fasting plasma glucose. The glucokinase activator piragliatin has an acute glucose-lowering action in patients with mild type 2 diabetes, mainly mediated through a generalized enhancement of beta-cell function and through fasting restricted changes in glucose turnover. Headache and mild hypoglycemia were the most frequent adverse events associated with piragliatin treatment. The effect of piragliatin treatment on the QTc interval was dose/exposure dependent following short-term multiple doses. Piragliatin had been in phase II clinical trial for the treatment of Type 2 diabetes mellitus. However, this development was discontinued.

GW842166 is a pyrimidine cannabinoid 2 (CB2) receptor agonist that was being developed by GlaxoSmithKline for the treatment of inflammatory pain. It has potent analgesic, anti-inflammatory and anti-hyperalgesic actions in animal models, but without cannabis-like behavioural effects due to its extremely low affinity for the CB1 receptor. GW842166 shows similar potency and efficacy for rat and human recombinant CB2 receptors with EC50 of 91 nM and 63nM, respectively. GW842166 is in Phase 2 trial.

ISPRONICLINE is a partial agonist at the a4b2 subtype of nicotinic acetylcholine receptors (nAChRs) without interaction with other nAChRs or other receptor systems. It has antidepressant, nootropic, and neuroprotective effects. It progressed to phase II clinical trials for the treatment of dementia and Alzheimer's disease but is no longer under development.

Valategrast (R-411) is a dual-acting α4/β1 - α4/β7 integrin antagonist which underwent clinical development with Roche for the treatment of multiple sclerosis (MS) and asthma. Phase I and II studies have been conducted. It had shown good efficacy in animal disease models. Following oral administration, R-411 was rapidly and completely biotransformed into its active metabolite, RO-0270608, most of which was eliminated by biliary excretion. R-411 had shown acceptable pharmacokinetics and good safety in healthy volunteers. R-411 inhibited eosinophil and T H 2 cell excitation and survival, and inhibited eosinophil migration from blood to pulmonary tissues. The idea of combining R-411 with montelukast (leukotriene antagonist) in the pharmaceutical dosage forms, therefore, provided a therapeutic treatment that had the combined effect of reducing circulating eosinophil counts and reducing eosinophil egress into pulmonary tissues, thereby providing an early onset of bronchodilation as well as sustained anti-inflammatory effects. Valategrast had been in phase II clinical trials by Roche for the treatment of asthma and in phase I clinical trials for the treatment of multiple sclerosis (MS). However, the study had been discontinued. Development of Valategrast was discontinued for the treatment of asthma after clarification of the regulatory framework for that class of compounds.

Lemildipine is a 1,4-dihydropyridine calcium channel blocker which is under phase III development by Banyu (Merck and Co), in Japan, for its potential to treat hypertension and cerebrovascular ischemia. In one study, involving five patients with essential hypertension accompanied by cerebrovascular disorder, lemildipine, administered orally at doses of 5 to 20 mg/day, significantly lowered blood pressure and increased cerebral blood flow. Another study in 31 patients with essential hypertension demonstrated that lemildipine has significant pressure lowering effects without affecting serum lipids. Worldwide rights to market the drug have been assigned to Kowa in Japan.

FEPENTOLIC ACID is a choleretic agent.

FENPIPRAMIDE is a parasympatholytic agent. As a hydrochloride salt, it is an active ingredient of some veterinary medicinal products used as analgesic drugs or antidotes. FENPIPRAMIDE was formerly used in humans as a spasmolytic in obstetrics.

Etanterol (VAL 481), a phenethanolamine derivative, is a β2 adrenoceptor agonist that was undergoing phase II trials in Italy as a bronchodilator with Valeas.