Sivelestat is a neutrophil elastase inhibitor approved in Japan and the Republic of Korea for acute lung injury, including acute respiratory distress syndrome in patients with systemic inflammatory response syndrome. Sivelestat is marketed as Elaspol in Japan. Sivelestat competitively inhibited human neutrophil elastase (IC50 = 0.044 uM, Ki = 0.2 uM). It also inhibited leukocyte elastase obtained from rabbit, rat, hamster and mouse.

Gabexate is a synthetic protease inhibitor, was shown to be effective in treating patients with sepsis-associated disseminated intravascular coagulation in which tumor necrosis factor-alpha (TNF-alpha) plays a critical role. Gabexate mesylate is a drug marketed only in Italy and Japan and it is considered an essential drug in the treatment of acute pancreatitis. Gabexate is marketed under the brand name REMINARON among others in Japan. It relieves inflammatory symptoms in the pancreas by inhibiting various enzymes. It also improves organ disorders and bleeding tendency caused by blood clots in blood vessels by inhibiting blood coagulation. It is usually used to treat acute pancreatitis with deviation of proteolytic enzymes (such as trypsin, kallikrein and plasmin), acute exacerbation of chronic recurrent pancreatitis, acute pancreatitis after surgery and disseminated intravascular coagulation.

Acefylline is a stimulant drug of the xanthine chemical class. It acts as an adenosine receptor antagonist. Acephylline piperazine is a theophylline derivative with a direct bronchodilator action. It has the advantages over theophylline in being far less toxic and producing minimal gastric irritation. It is indicated for the treatment of asthma, emphysema, acute and chronic bronchitis associated with bronchospasm.Acefylline relaxes smooth muscles, relieves bronchospasm & has a stimulant effect on respiration. It stimulates the myocardium & central nervous system, decreases peripheral resistance & venous pressure & causes diuresis. The mechanism of action is still not clear, inhibition of phosphodiesterase with a resulting increase in intracellular cyclic AMP does occur, but not apparently at concentrations normally used for clinical effect. Other proposed mechanisms of action include adenosine receptor antagonism, prostaglandin antagonism & effects on intracellular calcium. Sodium phenobarbital is a non-selective central nervous system depressant that is primarily used as sedative-hypnotic.

Acedia Sulfone, an antimicrobial drug that is a prodrug of dapsone, which is used to treat leprosy.

Nalfurafine, an opioid κ-selective agonist, has been officially approved for resistant pruritus in HD patients on the basis of a well-evidenced clinical trial in Japan. Nalfurafine hydrochloride is a potent and selective agonist for mouse, rat, guinea pig, and human κ-opioid receptors without significant activity on µ- and δ-opioid receptors. Nalfurafine hydrochloride (2.5 and 5 ug/day) has been proven to be safe and effective for the treatment of HD patients with uremic pruritus resistant to antihistamines.

Developed by Solvay Pharmaceuticals, cilansetron is a 5-HT3 antagonist indicated for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS). 5-HT(3) receptor antagonists such as cilansetron have been shown to affect gastrointestinal motility. With Phase III registration trials on cilansetron completed, Solvay filed for regulatory approval in Europe and the US in 2004. To ensure that cilansetron is only prescribed to patients with diarrhoea-predominant IBS, Solvay’s regulatory submission included an extensive appropriate use plan. In April 2005, however, Solvay received a “non-approvable” letter from the FDA and a request for additional data to support product registration in the US. Towards the end of 2005, the company announced that it had suspended registration of cilansetron in the US. Meanwhile, discussions continue with the UK’s MHRA about European marketing approval for cilansetron. In 2005, the MHRA also declined to approve cilansetron. Both the agencies requested additional clinical data to further assess the risk-benefit ratio of the compound. Despite the drug being rejected for approval, Solvay believed in the product and felt that the clinical data demonstrated important benefits for men and women suffering from diarrhoea-predominant IBS. However, taking into account the amount of clinical work requested and other business considerations, the company decided to end the development and regulatory activities for cilansetron. The clinical efficacy and safety of cilansetron was established in a series of clinical trials, including a large-scale international Phase III programme involving over 4,000 patients. Overall, results from these trials showed that cilansetron is significantly more effective than placebo in male and female patients with diarrhoea-predominant IBS, an important finding given the traditionally high placebo response rates seen in clinical trials of IBS drugs. Overall responder rates (adequate relief in at least 50% of weekly responses) for patients treated with cilansetron ranged from 52% to 61% compared with 37% to 46% for placebo recipients. The most common side effect of cilansetron is constipation, which is seen in 3-12% of subjects at 6 months. Ischemic colitis, a side effect associated with previous drugs of this class, has been seen in eight subjects (six women and two men) to date. All of these ischemic colitis events have been self-limited and did not require surgery. Because of its high degree of efficacy, the fact that it was well tolerated by the overwhelming majority of patients and that it showed efficacy in both genders, cilansetron represented a major advance in the treatment of irritable bowel syndrome with diarrhea predominance.

Aceclidine is a parasympathomimetic agent used in the treatment of open-angle glaucoma as topical eye drop solution. It is as a muscarinic acetylcholine receptor agonist with weak anticholinesterase activity. Acting directly on the motor end-plate (cholinergic nerve endings) it decreases intraocular pressure and mediates the contraction of iris muscle. Aceclidine increased outflow facility in human eyes in vitro by a direct stimulation of the outflow tissues in the absence of an intact ciliary muscle. This effect was biphasic, occurring at concentrations of 10 uM and lower with no effect at higher concentrations. Passed numerous clinical trials in Russia, France, Italy and other countries and was widely used in Europe but never been in clinical use in USA.

Acecainide (N-acetylprocainamide), the N-acetylated metabolite of procainamide, is a Class III antiarrhythmic agent. Acecainide exerts cardiac anticholinergic effect. It elicits smooth muscle relaxation mainly through the activation of plasma membrane K+ channels. Acecainide markedly reduced premature ventricular beats and prevented induction of ventricular tachycardia. Acecainide appears to offer advantages over procainamide, particularly with respect to the reduced formation of antinuclear antibodies. Acecainide development has been discontinued.

Perhexiline, 2-(2,2-dicyclohexylethyl)piperidine, is an anti-anginal drug. Perhexiline reduces fatty acid metabolism through the inhibition of carnitine palmitoyltransferase, the enzyme responsible for mitochondrial uptake of long-chain fatty acids. Perhexiline is used for reducing the frequency of moderate to severe attacks of angina pectoris due to coronary artery disease in patients who have not responded to other conventional therapy or in whom such therapy may be contraindicated. Heart Metabolics Limited is developing perhexiline for the treatment of hypertrophic cardiomyopathy

Zuclopenthixol is indicated the management of the manifestations of schizophrenia and other mental illnesses with disturbances in thinking, emotional reactions and behaviour. It is also used to treat the manic phase of manic depressive illness. Zuclopenthixol, a thioxanthene derivative, has high affinity for both dopamine D1 receptors and dopamine D2 receptors. Zuclopenthixol also has high affinity for α1-adrenergic and 5-HT2 receptors. Zuclopenthixol (CLOPIXOL®) is avavilable in the form of tablets and solution for intramuscular injections.