FLUDAZONIUM is a topical antiinfective agent.

Telcagepant (MK-0974) is a calcitonin gene-related peptide receptor antagonist. Merck & Co was developing telcagepant for the treatment of pain. Telcagepant is an extremely potent CGRP antagonist with a Ki = 0.77 (0.07 nM). Telcagepant showed efficacy against acute migraines; however, different patient populations may show more beneficial effects with telcagepant versus triptans. In the acute treatment of migraine, Telcagepant was found to have equal potency to rizatriptan and zolmitriptan in two Phase III clinical trials. Merck & Co has now terminated development of the drug.

Eritoran (E-5564) is a synthetic lipid A analog that has been designed to antagonize the effects of lipopolysaccharide (LPS) and has been found to do this by interacting with Toll-like receptor 4, the cell surface receptor for LPS. Preclinical in vitro and in vivo studies of eritoran tetrasodium indicate it can limit excessive inflammatory mediator release associated with LPS and improve survival in sepsis models. Clinically, eritoran was being investigated for the treatment of severe sepsis, septic shock, and other endotoxin-mediated indications. Eritoran development has been discontinued.

Vapitadine (R129160; Hivenyl™) is an antihistamine that Barrier Therapeutics is developing as a treatment for allergic reactions of the skin, such as those associated with hives and for the itch associated with atopic dermatitis. Vapitadine is a new selective, non-sedative H1antihistamine. In several in vitro and in vivo pharmacological models, vapitadine is at least as potent as cetirizine (Zyrtec®) and does not penetrate the blood-brain barrier. An advantage of vapitadine over other antihistamines may be the absence of the sedation, even at high doses. Vapitadine had been in phase II clinical trials for the treatment of patients with atopic dermatitis. However, no development has been reported.

Mivobulin is a synthetic water-soluble colchicine analog with the broad antitumor activity that competitively binds tubulin at the colchicine-binding site and inhibits tubulin polymerization. Cancer cells exposed to Mivobulin isethionate accumulate in the M phase of the cell cycle and subsequently die. Preclinical studies have demonstrated that Mivobulin isethionate is able to cross the blood-brain barrier. Importantly, Mivobulin isethionate demonstrated significant antitumor activity in a broad spectrum of murine and human tumor models that were cross-resistant to vincristine, cisplatin, vinblastine, navelbine, and doxorubicin and in tumor cell lines exhibiting multidrug resistance owing to P-glycoprotein overexpression. In animal studies, the activity of Mivobulin isethionate was largely independent of the route of drug administration but favored a prolonged treatment schedule. Unfortunately, in clinical trials, Mivobulin fail to demonstrate the significant activity

Elantrine is an anticholinergic drug. Elantrine has been investigated in the treatment of parkinsonism.

Intoplicine is a pyrido[4,3-b]indole derivative patented by Rhone-Poulenc Sante as an antitumor agent. Intoplicine acts via inhibiting DNA nicking and closing reactions by stabilizing the cleavable complex, a transient intermediate in the religation reaction involving topoisomerase I and II and DNA. Intoplicine was active in a range of solid tumors in mice, including colon adenocarcinoma 51, MA16/C, MA14/A, MA13/C, early-stage pancreatic ductal adenocarcinoma 03, Glasgow osteogenic sarcoma and B16 melanoma. In Phase I clinical studies using a 24-h infusion, the maximum tolerated dose was established as 270 mg/m2 every 3 weeks, with hepatotoxicity rather than myelosuppression being dose-limiting, although cardiac toxicity was also seen. Preclinical cytotoxic concentrations were not achieved at the dose levels studied and clinical development was discontinued.

Carvotroline [WY 47791] is a novel γ-carboline derivative with a preclinical profile suggestive of antipsychotic activity. Carvotroline has an affinity for the dopamine D2 receptor and cortical 5-HT2 receptor that is ten times greater than serotonin. Carvotroline administration to rats leads to a decrease of plasma corticosterone levels and demonstrated a moderating effect on the rotational-stress induced rise in plasma corticosterone levels.

ISOMOLPAN is a selective D3/D2 receptor agonist.