Topiramate, sold under the brand name Topamax among others, is a medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence and essential tremor. For epilepsy this includes treatment for generalized or focal seizures. It is taken orally.
Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for Chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.
Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term neurosteroid was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term, neuroactive steroid refers to steroids that can be synthesized in the brain, or are synthesized by an endocrine gland, that then reach the brain through the bloodstream and have effects on brain function. The term neuroactive steroids was first coined in 1992 by Steven Paul and Robert Purdy. In addition to their actions on neuronal membrane receptors, some of these steroids may also exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a wide range of potential clinical applications from sedation to treatment of epilepsy and traumatic brain injury. Ganaxolone, a synthetic analog of the endogenous neurosteroid allopregnanolone, is under investigation for the treatment of epilepsy.
Denileukin diftitox was an antineoplastic agent, an engineered protein combining interleukin-2 and diphtheria toxin. Denileukin diftitox could bind to interleukin-2 receptors and introduce the diphtheria toxin into cells that express those receptors, killing the cells. In some leukemias and lymphomas, malignant cells express these receptors, so denileukin diftitox can target these.
Lasofoxifene, sold under the brand name Fablyn, is a nonsteroidal selective estrogen receptor modulator (SERM) which is marketed by Pfizer in Lithuania and Portugal for the prevention and treatment of osteoporosis and for the treatment of vaginal atrophy, and the result of an exclusive research collaboration with Ligand Pharmaceuticals (LGND). It also appears to have had a statistically significant effect of reducing breast cancer in women according to a study published in The Journal of the National Cancer Institute.
Tebanicline is a potent synthetic nicotinic (non-opioid) analgesic drug developed by Abbott. It was developed as a less toxic analog of the potent poison dart frog-derived compound epibatidine, which is about 200 times stronger than morphine as an analgesic, but produces extremely dangerous toxic side effects. Like epibatidine, tebanicline showed potent analgesic activity against neuropathic pain in both animal and human trials, but with far less toxicity than its parent compound. It acts as a partial agonist at neuronal nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes.
ELB-139 (LS-191,811) is an anxiolytic drug with a novel chemical structure, which is used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.
Caroverine is a muscle-relaxing drug used in Austria and Switzerland to relieve spasms in smooth muscles, and the use in those countries was extended to aid with cerebrovascular diseases there, and eventually to treat tinnitus. It is also used to treat tinnitus in India.
Naluzotan is a serotonergic drug of the phenylpiperazine class that was under investigation by EPIX Pharmaceuticals Inc for the treatment of generalized anxiety disorder and major depressive disorder. It acts as a selective and potent 5-HT1A receptor partial agonist, readily stimulating prolactin responses, though it has also been found to bind to and activate the σ receptor. Naluzotan was well tolerated in clinical trials, with more patients in the control group dropping out due to adverse effects than in the active group in one study. The most frequently reported side effect was headache in 15% of patients. In addition, naluzotan demonstrated significant antidepressant and anxiolytic effects as per the HAM-D and MADRS and the HAM-A, respectively, in some trials, but in others it did not. In the end it was not found to be significantly superior enough to placebo and development was stopped.
Trimegestone, sold under the brand names Ondeva and Totelle among others, is a progestin medication which is used in menopausal hormone therapy and in the prevention of postmenopausal osteoporosis. It was also under development for use in birth control pills to prevent pregnancy, but ultimately was not marketed for this purpose. The medication is available alone or in combination with an estrogen. It is taken by mouth.
Tazomeline (LY-287,041) is a drug which acts as a non-selective muscarinic acetylcholine receptor agonist. It was in clinical trials for the treatment of cognitive dysfunction such as that seen in Alzheimer's disease and schizophrenia, but development was apparently scrapped for unknown reasons. Another of the patented uses is for the treatment of "severe painful conditions".
Fedotozine is an opioid drug which acts as a peripherally specific selective κ1-opioid receptor agonist with preference for the κ1A subtype. It was under investigation for the treatment of gastrointestinal conditions like irritable bowel syndrome and functional dyspepsia and made it to phase III clinical trials, but ultimately development was discontinued and it was never marketed.
Rosonabant (INN; E-6776) is a drug acting as a CB1 receptor antagonist/inverse agonist that was under investigation by Esteve as an appetite suppressant for the treatment of obesity. Development of the drug for clinical use was apparently halted shortly after the related CB1 antagonist rimonabant was discontinued in November 2008, due to the reports of severe psychiatric adverse effects such as anxiety, depression, and suicidal ideation associated with it and with similarly acting agents.
Samidorphan is an opioid antagonist that in the form of olanzapine/samidorphan is used in the treatment of schizophrenia and bipolar disorder. Samidorphan reduces the weight gain associated with olanzapine. Samidorphan is taken by mouth.
Selurampanel is a drug closely related to the quinoxalinedione series which acts as a competitive antagonist of the AMPA and kainate receptors and, as of 2015, is being investigated in clinical trials by Novartis for the treatment of epilepsy. It has also been studied in the acute treatment of migraine, and was found to produce some pain relief, but with a relatively high rate of side effects.
Irampanel is a drug which acts as a dual noncompetitive antagonist of the AMPA receptor and neuronal voltage-gated sodium channel blocker. It was under development by Boehringer Ingelheim for the treatment of acute stroke/cerebral ischemia but never completed clinical trials for this indication. Irampanel was also trialed, originally, for the treatment of epilepsy and pain, but these indications, too, were abandoned, and the drug was ultimately never marketed.
Neboglamine (INN), formerly known as nebostinel, is a positive allosteric modulator of the glycine site of the NMDA receptor which is under investigation for Rottapharm for the treatment of schizophrenia and cocaine dependence. It shows cognition- and memory-enhancing effects in animal models. As of June 2015, it is in phase II clinical trials for both schizophrenia and cocaine abuse.
Examorelin (INN) (developmental code names EP-23905, MF-6003), also known as hexarelin, is a potent, synthetic, peptidic, orally-active, centrally-penetrant, and highly selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and a growth hormone secretagogue which was developed by Mediolanum Farmaceutici. It is a hexapeptide with the amino acid sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2 which was derived from GHRP-6. These GH-releasing peptides have no sequence similarity to ghrelin, but mimic ghrelin by acting as agonists at the ghrelin receptor.
Bevenopran is a peripherally acting μ-opioid receptor antagonist that also acts on δ-opioid receptors and was under development by Cubist Pharmaceuticals for the treatment of chronic opioid-induced constipation. It reached phase III clinical trials for this indication before being discontinued.
An endocannabinoid enhancer (eCBE) is a type of cannabinoidergic drug that enhances the activity of the endocannabinoid system by increasing extracellular concentrations of endocannabinoids. Examples of different types of eCBEs include fatty acid amide hydrolase (FAAH) inhibitors, monoacylglycerol lipase (MAGL) inhibitors, and endocannabinoid transporter (eCBT) inhibitors. An example of an actual eCBE is AM404, the active metabolite of the analgesic paracetamol and a dual FAAH inhibitor and eCBRI.
