Diethylhomospermine is the polyamine analogue. It suppressed the activity of the major biosynthetic enzymes, ornithine decarboxylase and S-adenosylmethionine decarboxylase in human bladder cancer cell lines. Diethylhomospermine given as the subcutaneous injection is overall well tolerated at lower doses, but significant toxicities were observed at the 37.5mg/m2/day dose level. Maximal tolerated dose was established at 25 mg/m2/day but further investigation with this study drug is not recommended secondary to the potential for neurotoxicities and hepatic damage as a result of cumulative doses. Diethylhomospermine had been in phase II clinical trials for the treatment of AIDS-related chronic diarrhea. However, this research has been discontinued.

3-Indolepropionic acid (IN-OX1; Indole-3-propionic acid; OX-1; Oxigon; SHP 22; SHP-622; VP-20629), an endogenous substance produced by bacteria in the intestine, is a deamination product of Tryptophan (T947200) that protects the hippocampus (studied in gerbils) from ischemic damage and oxidative stress. It’s ability to protect the neurons in this way is attributed to its potent antioxidative effects. 3-Indolepropionic acid is also hypothesized to have protective effects on the thyroid gland. 3-Indolepropionic acid is being studied for therapeutic use in Alzheimer's disease. 3-Indolepropionic acid (IPA) completely protected primary neurons and neuroblastoma cells against oxidative damage and death caused by exposure to Abeta, by inhibition of superoxide dismutase, or by treatment with hydrogen peroxide. In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity. In 2011, Intellect redirected the focus of the OX1 program from Alzheimer's disease to FA (Friedreich's Ataxia). Research suggests that the symptoms associated with FA are the result of oxidative stress caused by the abnormal accumulation of iron. OX1's ability to neutralize ROS could be an effective agent to reduce oxidative stress in FA, thereby eliminating the symptoms of FA and increasing both quality of life and longevity in affected individuals.

Alseres Pharmaceuticals is developing an 123I-labelled imaging agent, Altropane®, as a diagnostic aid in Parkinson's disease and other movement disorders. Altropane is a molecular-imaging agent that specifically binds to the dopamine transporter (DAT) protein found on the surface of dopamine-producing neurons, making it visible during SPECT imaging. Since most forms of Parkinsonian Syndromes result in a decreased number of dopamine-producing cells, it would be expected that these patients also have fewer DATs than do patients without PS. Thus, it is believed that altropane used in conjunction with SPECT imaging could be a useful test to distinguish Parkinsonian Syndrome tremors from non-Parkinsonian tremor: non-Parkinsonian patients would have more altropane-binding visible in the SPECT image, while Parkinsonian patients would have less. The E isomer of (123)I-2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(1-iodoprop-1-en-3-yl)nortropane (Altropane(R)) shows high affinity (IC(50) = 6.62 +/- 0.78 nmol) and selectivity (DA/5-HT = 25) for DAT sites in the striatum. Altropane is presently in Phase III clinical development for the diagnosis of Parkinson's disease.

10-Hydroxycamptothecin (10-HCPT), an indole alkaloid isolated from a Chinese tree, Camptotheca acuminate, inhibits the activity of topoisomerase I and has a broad spectrum of anticancer activity in vitro and in vivo. However, its use has been limited due to its water-insolubility and toxicity with i.v. administration. Prolonged elimination of 10-HCPT in vivo may have a significant impact on its therapeutic effects. 10-HCPT is metabolized to its carboxylate form and glucuronides.It was investigated that relatively low dose of 10-HCPT is able to inhibit the growth of colon cancer, facilitating the development of a new protocol of human trials with this anticancer drug.

Ravatirelin is a thiazolyl-alanine derivative patented by Japanese pharmaceutical company Shionogi & Co., Ltd. as a thyrotropin-releasing compound with improved central nerve activating effects such as sustained acetylcholine-releasing effect, and spontaneous motility increasing effect. Rovatirelin binds to the human thyrotropin-releasing hormone receptor with nanomolar affinity and increases the spontaneous firing of action potentials in the acutely isolated noradrenergic neurons of rat locus coeruleus. In in vivo studies, oral administration of Ravatirelin increased both c-Fos expression in the LC and extracellular levels of noradrenaline in the medial prefrontal cortex of rats. Furthermore, Ravatirelin increased locomotor activity. The increase in noradrenaline level and locomotor activity by Ravatirelin was more potent and longer acting than those by taltirelin. In phase I studies in healthy adult males, Ravatirelin exhibited linear pharmacokinetics in a single-ascending dose (0.1 to 10 mg) and a benign safety profile supportive of once-daily oral administration. From results of Phase II and III studies to evaluate the efficacy and safety of Ravatirelin in spinocerebellar degeneration patients, a daily dose of 1.6 to 3.2 mg of Ravatirelin has been considered to be dosage level intended for clinical use as once-daily oral administration.

Burixafor is an orally bioavailable inhibitor of CXC chemokine receptor 4 (CXCR4) with receptor binding and hematopoietic stem cell-mobilization activities. Burixafor binds to the chemokine receptor CXCR4, thereby preventing the binding of stromal derived factor-1 (SDF-1 or CXCL12) to the CXCR4 receptor and subsequent receptor activation; this may induce the mobilization of hematopoietic stem and progenitor cells from the bone marrow into the blood. CXC motif chemokine receptor 4 (CXCR4) blockade is pursued as an alternative to mesenchymal stem cell treatment after heart transplantation. The augmentation of conventional mycophenolate mofetil plus corticosteroids with a CXCR4 antagonist is potentially effective in improving outcomes after heart transplantation in humans

Ordopidine (also known as ACR-325) is a dopaminergic stabilizer that acts as dopamine D2 receptor antagonists with low affinity. Ordopidine under the development of NeuroSearch participated in phase I trials for the treatment of Parkinson's disease and bipolar disorder. Information about the current study of this drug is not available.

Saniona was developing seridopidine (also known as ACR343), a modulator of dopaminergic activity, as an orally administered therapy for schizophrenia, Tourette's syndrome and parkinson's disease. Seridopidine is a modulator of dopaminergic activity.