Frentizole, a nontoxic antiviral and immunosuppressive agent, was used clinically in rheumatoid arthritis and systemic lupus erythematosus. Frentizole was more effective in suppressing human lymphocytes responding to Con A and PWM, than it was in cells activated by PHA, specific antigen, or alloantigen. Methylprednisolone, on the other hand, was more inhibitory for cells stimulated by PHA, specific antigen, or alloantigen. Frentizole, even at super immunosuppressive doses, does not predispose the hose (mice) to Pseudomonas aeruginosa, Candida albicans, herpes simplex virus, or Ann Arbor influenza virus. Frentizole is an inhibitor of the Aβ-ABAD interaction.

Roquinimex (Linomide, LS 2616) is a quinoline-3-carboxamide with pleiotropic immune modulating capacity and it has therapeutic effects in several experimental animal models of autoimmune diseases. Linomide has been evaluated in clinical trials for multiple sclerosis, and was indeed shown to have disease inhibitory effects. However, due to unexpected side effects recorded in patients treated with Linomide, premature termination of clinical trials was required. The basic mechanism(s) of action of Linomide in inducing beneficial effects in autoimmune diseases is still elusive. Some experimental evidence indicates that Linomide influences the regulation of the cytokine profile, resulting in the inhibition of autoimmune and inflammation pathologies. Roquinimex possesses potential antineoplastic activity. Roquinimex inhibits endothelial cell proliferation, migration, and basement membrane invasion; reduces the secretion of the angiogenic factor tumor necrosis factor alpha by tumor-associated macrophages (TAMs); and inhibits angiogenesis. Roquinimex was in phase III clinical trials with Pharmacia Corporation in Europe and the US for the treatment of multiple sclerosis.

Amithiozone, also known as thioacetazone, is an oral antibiotic, which is used in the treatment of tuberculosis. In 1991, the World Health Organization (WHO) recommended replacing thioacetazone with ethambutol in patients with known or suspected HIV infection. Thioacetazone is no longer included in WHO’s recommended first-line treatment for tuberculosis and is now reserved for uncommon situations in which treatment options have been compromised by resistance to other anti-tuberculosis medicines in HIV-negative individuals. Despite the increased recognition of this risk, thioacetazone remained in use mainly in low-income countries because of its low cost. Amithiozone has also been used in trials studying the treatment of Mycobacterium Avium-intracellular Infection. One of the possible mechanism action of the drug is interference with the metabolism of methionine of susceptible tubercle bacilli, which utilize methionine for nucleic acid synthesis.

Armin is irreversible cholinesterase inhibitor. It acts considerably longer and stronger than reversible cholinesterase inhibitors. It is used for glaucoma treatment. Armin might be used in combination with other antiglaucoma drugs. Known adverse effects are: hypersalivation, sweating, dyspepsia, frequent urination, blurred vision, headache, dizziness, twitching of the tongue and skeletal muscles, nausea, vomiting.

Delamanid (OPC-67683, Deltyba™) is a nitro-dihydro-imidazooxazoles derivative. It is a mycolic acid biosynthesis inhibitor, an essential component of the cell wall of M. tuberculosis. Delamanid possess highly potent activity against tuberculosis, as shown by its exceptionally low minimum inhibitory concentration range in vitro and highly effective therapeutic activity at low doses in vivo. Delamanid has been developed by Otsuka Pharmaceutical for the treatment of multidrug-resistant tuberculosis. Delamanid received its first global approval for the treatment of MDR-TB in the European Union (EU), for use in combination with optimised background therapy. It is also under review for marketing in Japan for MDR-TB, the first drug application filed in Japan for this indication. Delamanid has been granted orphan drug status in both the EU and Japan.

Pizotifen (INN) or pizotyline (USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventative to reduce the frequency of recurrent migraine headaches. Pizotifen is a serotonin antagonist acting mainly at the 5-HT2A and 5HT2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity. The main medical use for pizotifen is for the prevention of vascular headache including migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propranolol, topiramate, valproic acid and amitriptyline. While pizotifen is reasonably effective, its use is limited by side effects, principally drowsiness and weight gain, and it is usually not the first choice medicine for preventing migraines, instead being used as an alternative when other drugs have failed to be effective. It is not effective in relieving migraine attacks once in progress. Pizotifen has also been reported as highly effective in a severe case of erythromelalgia, a rare neurovascular disease that is sometimes refractory to the other drugs named above. Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain. Occasionally it may cause nausea, headaches, or dizziness. In rare cases, anxiety, aggression and depression may also occur. Pizotifen is well absorbed from the gastro-intestinal tract, peak plasma concentrations occurring approximately 5 hours after oral administration. The absorption of pizotifen is fast (absorption half life 0.5 to 0.8 hours) and nearly complete (80%). Over 90% is bound to plasma proteins. Pizotifen undergoes extensive metabolism. Over half of a dose is excreted in the urine, chiefly as metabolites; a significant proportion is excreted in the faeces. The primary metabolite of pizotifen (N-glucuronide conjugate) has a long elimination half-life of about 23 hours.

Proroxan is a non-selective а-adrenoblocker. Proroxan was found to prevent the development of hypertensive crises and improve cerebral bioelectrical parameters in most of hypertensive patients. Proroxan has been used as an antihypertensive and in the treatment of Ménière’s disease, motion sickness, and allergic dermatitis.

Ethyl fumarate is an anti-psoriatic agent. Its salts are used for the treatment of severe psoriasis (Fumaderm formulation). The mechanism of its action is unknown.

Veralipride (trade name Agreal, Agradil) is a benzamide neuroleptic medicine indicated in the treatment of vasomotor symptoms associated with the menopause when a contraindication or non-acceptance of hormone therapy (HT) exists. Veralipride is a dopaminergic antagonist of receptor D2, that induces prolactin secretion without any estrogenic or progestagenic effects. Veralipride is well absorbed when administered orally, achieving maximal concentrations at 2.5 hours. It is poorly metabolized and is eliminated in the urine and feces. After oral administration, the half-life is 4 hours, and 44% is excreted without any changes in urine in the first 120 hours. Most of the studies agree that the decrease of vasomotor symptoms associated with the menopause (hot flushes) with veralipride use is from 48.0% to 89.9% depending on the time of use and method of administration. One of the main secondary effects of veralipride use is hyperprolactinemia, which may or may not be accompanied by galactorrhea, and can disappear at 48 hours of treatment withdrawal. The most serious effects that have been reported with veralipride use are those extrapyramidal, such as acute dyskinesia, tardive dyskinesia, Parkinsonism, postural tremor, myoclonia, and dystonia. Many of these have been related to over-dosage and due to the lack of prescription instruction follow-up. The presentation of secondary adverse events is decreased using this medicament at a dose no greater than 100 mg/day, for short time spans, and leaving drug-free intervals between schedules. Veralipride has never gained approval in the United States. On July 2007, the EMA recommended the withdrawal of marketing authorizations for veralipride. The still in use Mexican Official Norm for the prevention and control of perimenopausal and postmenopausal diseases in women establishes that the drug can be useful in the control of vasomotor symptoms.

Bupranolol is a non-selective beta blocker without intrinsic sympathomimetic activity (ISA), but with strong membrane stabilizing activity. Bupranolol competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart, inhibiting sympathetic stimulation. This results in a reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension. Ophthalmic Bupranolol is used for the management of glaucoma and oral Bupranolol is used for the management of cardiovascular disorders. S-Bupranolol has also being shown to have superior preclinical safety profile and great antinociceptive efficacy and should be considered as a unique b-AR compound to advance future clinical pain studies.