Linopirdine [DuP 996, 3, 3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one], a putative cognition enhancing drug, increases acetylcholine release in rat brain tissue and improves performance in animal models of learning and memory. Linopirdine was developed as a cognitive enhancing molecule and demonstrated to specifically block the potassium current generated by the brain specific KCNQ2-KCNQ3 proteins (M-channel). Linopirdine also acts as an agonist of TRPV1. At low concentrations linopirdine sensitizes both recombinant and native TRPV1 channels to heat, in a manner that is not prevented by the Kv7-channel opener flupirtine. Taken together, these results indicate that linopirdine exerts an excitatory action on mammalian nociceptors not only through inhibition of the M current but also through activation of the capsaicin receptor TRPV1. In the late 1980s, DuPont initiated clinical trials with linopirdine for Alzheimer’s disease. Linopirdine was regarded as a promising drug because it enhanced the release of acetylcholine in cholinergic nerve terminals in the brain only when its release was triggered and improved learning and memory in rodents and primates. Although clinical trials with linopirdine remained largely inconclusive or showed that it did not improve memory performance in elderly subjects, linopirdine became a valuable pharmacological tool. Development of Linopirdine for the treatment of Alzheimer's disease was discontinued.

Vinflunine (Javlor) is the first fluorinated microtubule inhibitor belonging to the Vinca alkaloids family. Vinflunine, at the lowest effective concentrations, interacts with the Vinca alkaloid binding site on tubulin, suppresses microtubule dynamics (switching at microtubule ends between phases of slow growth and rapid shortening) and microtubule treadmilling (growth at the plus end and shortening at the minus end of the microtubule), causes cell cycle arrest which appears on fluorescence-activated cell sorting analysis as a G2 + M phase arrest, and is associated with an accumulation of cells in mitosis leading to cell death via apoptosis. Vinflunine has been been approved for advanced or metastatic transitional cell carcinoma of the urothelial tract. Pierre Fabre submitted an extension to the EU authorisation to add treatment of advanced breast cancer.

Cadralazine is an antihypertensive of the hydrazinophthalazine chemical class. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. The therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.

Naftazone is a naphtoquinone derivative which was originally registered in several European countries for treating symptoms of varicose veins and venous insufficiency, based on its venoconstrictive properties. ts venotonic mechanism of action remains unknown, but the drug has anti‐inflammatory effects and inhibits platelet aggregation. Naftazone is shown to accelerate human saphenous vein endothelial cell proliferation in vitro at concentrations which did not alter the hemostatic balance. Naftazone, which exhibits glutamate release inhibition properties, has shown antiparkinsonian and antidyskinetic activity in preclinical models of Parkinson's disease and in a clinical proof of concept study. Naftazone is currently marketed in several countries.

Laquinimod is a new orally available carboxamide derivative, which is currently developed for relapsing remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative diseases. The mechanism of action of laquinimod is not fully elucidated because the molecular target is not known. Treatment with laquinimod led to a significant and persistent increase in brain-derived neuroprotective factor (BDNF) serum levels compared to placebo treatment. In human studies, a decrease of pro-inflammatory and an increase of anti-inflammatory cytokines have been measured. After commercial launch the unexpected severe cardiac adverse events (AEs) such as serositis, pericarditis, and myocardial infarction were detected.

Mesulfen is a drug that was used for the treatment of seborrhea, seborrheic eczema and acne. Now the drug is presumably withdrawn from the market.

Fenoverine is a potent musculotropic, the anti-spasmodic agent that restores smooth muscle motility and relieves the distressing symptoms associated with irritable bowel syndrome (IBS) and primary dysmenorrhea. Fenoverine is a non-anticholinergic phenothiazine derivative that may also inhibit calcium channel currents. Fenoverine primarily affects the gastrointestinal tract, bile duct, and female genital organs. Fenoverine has been repeatedly implicated in the occurrence of rhabdomyolysis, a potentially fatal adverse effect, in France. Thes drug has been therefore unavailable in France since December 1995 but commonly used in the treatment of gastrointestinal spasmodic disorders in Taiwan.

Garenoxacin is an antibacterial agent active against a range of aerobic Gram-positive and Gram-negative bacteria. It exerts its action by inhibiting bacterial DNA gyrase and topoisomerase IV. The drug was withdrawn from the market in Europe and was never approved in the USA. Garenoxacin is still marketed in Japan under the name Geninax.

Valpromide (2-propylpentanamide) is a derivative of valproic acid. Bio-pharmacological data show several possible mechanisms of action involving an increase in GABA levels in brain as well as changes in membrane conductance on neurons. Valpromide has been shown to decrease aggressivity in stress-induced animals, to regulate anxious induced behaviours, as well as to potentiate central sedative compounds. It produces a significant increase of cognitive functions. Psychopathological experiments have shown: a wakening of personality, euphoric effects, an improvement of social behaviour, a stabilization of mood in affective disorders. Valpromide is indicated for the treatment of bipolar disorder (manic episodes). It is marketed in some Europe countries.

Rokitamycin is a macrolide antibiotic against Gram-positive bacteria. Synthesized from strains of Streptomyces kitasatoensis. Rokitamycin is an inhibitor of protein synthesis by specifically binding to the 50 S subunit of the ribosome. Specificity towards prokaryotes relies upon the absence of 50S ribosomes in eukaryotes.