Darglitazone is a member of the thiazolidinedione class of drugs and an agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), an orphan member of the nuclear receptor superfamily of transcription factors. It has a variety of insulin-sensitizing effects, such as improving glycemic and lipidemic control, and is used in the treatment of metabolic disorders such as type II diabetes. Darglitazone sodium had been in phase I clinical trials by Pfizer for the treatment of type 2 diabetes. However, this study has been discontinued.

Enadoline (CI-977) is a potent and selective agonist at the kappa-opioid receptor. Enadoline is a potent antinociceptive agent. Clinical use of enadoline was associated with dose-limiting neuropsychiatric adverse events. Enadoline may yet find some application against ischaemic stroke and severe head injury, presumably in comatose patients.

Efegatran (GYKI 14766; LY 294468) is a tripeptide D-methyl-phenylalanyl-prolyl-arginal thrombin inhibitor. It was developed by IVAX for the potential treatment of thromboembolic disorders, mainly myocardial infarction. However, information about the further development is not available.

Thiorphan is the first potent synthetic inhibitor of enkephalinase. Thiorphan displays antinociceptive activity after systemic administration. Thiorphan also inhibits to a lesser extent the widely distributed angiotensin-converting enzyme, a carboxydipeptidase implicated in blood pressure regulation. Thiorphan failed to potentiate allergen-induced airway responses in asthma. Thiorphan significantly reduced the castor oil-induced diarrhea in rats when administered intravenously but not when administered intracerebroventricularly. Racecadotril, via its active metabolite thiorphan, was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility.

Bemarinone (ORF 16600) is a positive inotropic and vasodilator agent with potential clinical utility in the management of congestive heart failure. The compound selectively and competitively inhibited cyclic AMP phosphodiesterase fraction III. However, further studies were discontinued

Iododoxorubicin is an anthracycline derivative patented by Farmitalia Carlo Erba S.p.A. for cancer treatment. In preclinical studies, Iododoxorubicin has demonstrated significantly reduced levels of cardiotoxicity compared to anthracyclines. Unfortunately, during phase II clinical trials Iododoxorubicin failed to demonstrate efficacy in an advanced breast cancer patient

Nanterinone [UK 61260], a phosphodiesterase III inhibitor, was undergoing II evaluation with Pfizer in the US for the treatment of heart failure. Nanterinone is a positive inotropic and balanced-type vasodilating drug, only partially based on phosphodiesterase III inhibition. Preliminary data from controlled studies suggest satisfactory long-term efficacy and safety.

Batelapine (or CGS 13429), an antipsychotic drug, that was undergoing preclinical development, but the further studied were discontinued

Lidorestat is a highly potent and selective aldose reductase inhibitor with good oral bioavailability that is reported to improve nerve conduction and reduce cataract formation. Lidorestat reduced mortality rates in hAR transgenic mice. Mice receiving lidorestat had similar survival rates as nonhAR-expressing diabetic mice. Lidorestat treatment did not affect plasma lipids, glucose, or weights of diabetic mice. Drugs such as lidorestat will improve human health by reducing the production of toxic products of the polyol pathway. Lidorestat was developed for the treatment of diabetic complications, including neuropathy, retinopathy, cataracts, nephropathy.

RGH-896 (radiprodi) is orally active and selective NMDA NR2B antagonist, a potential therapeutic agent in treatment of neuropathic pain and possibly other chronic pain conditions. It blocks pain signaling without interacting with other NMDA receptor subtypes thus potentially improving therapeutic index and side effect profile. RGH-896 is the first of this group and is currently in early clinical development. Forest and Richter initiated a Phase IIb study in neuropathic pain in the United Stated in the second half of 2006. The drug did not produce significant reductions in patient-reported pain scores for all the dosages tested. Forest says that it and Gedeon Richter will review the findings before making a decision about the further development of radiprodil. In addition to neuropathic pain, the companies intend to investigate various other pain conditions and possibly CNS indications not related to pain. Forest will pay Richter undisclosed upfront and milestone payments in addition to royalties and will have exclusive rights in the U.S. and Canada. The two companies will jointly fund the development program. RGH-896 has patent applications that provide patent protection until at least 2022.