Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesophageal reflux disease. It is also used to treat migraine headaches.
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes.
Memantine is a medication used to treat moderate-to-severe Alzheimer's disease. It is less preferred than acetylcholinesterase inhibitors such as donepezil. Treatment should only be continued if beneficial effects are seen. It is taken by mouth.
Rotigotine, sold under the brand name Neupro among others, is a dopamine agonist of the non-ergoline class of medications indicated for the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS). It is formulated as a once-daily transdermal patch which provides a slow and constant supply of the drug over the course of 24 hours.
Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic cardiac muscle is stiffer and less compliant and is seen in the progression to heart failure. The description below focuses on a specific mechanism of valvular pathology but there are other causes of valve pathology and fibrosis of the cardiac muscle.
5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT).
The 5HT6 receptor is a subtype of 5HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5HT). It is a G protein-coupled receptor (GPCR) that is coupled to Gs and mediates excitatory neurotransmission. HTR6 denotes the human gene encoding for the receptor.
Terguride, sold under the brand name Teluron, is a serotonin receptor antagonist and dopamine receptor agonist of the ergoline family. It is approved for and used as a prolactin inhibitor in the treatment of hyperprolactinemia in Japan. Terguride is taken by mouth.
Pimavanserin , sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis and is also being researched for the treatment of Alzheimer’s disease psychosis, schizophrenia, agitation, and major depressive disorder. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist.
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.
Capeserod (INN; development code SL65.0155) is a selective 5-HT4 receptor partial agonist with Ki = 0.6 nM and IA = 40–50% (relative to serotonin). It potently enhances cognition, learning, and memory, and also possesses antidepressant effects. Capeserod was in phase II clinical trials around 2004–2006 for the treatment of memory deficits and dementia but no new information has surfaced since and it appears to have been abandoned.
PRX-07034 is a selective 5-HT6 receptor antagonist. It has cognition and memory-enhancing properties and potently decreases food intake and body weight in rodents. PRX-07034 was under development by Epix Pharmaceuticals for the treatment of obesity and cognitive impairment associated with Alzheimer's disease and schizophrenia but upon the company collapsing due to lack of funds the compound was auctioned to another corporation.
PRX-08066 is a drug discovered and developed by Predix Pharmaceuticals [Dale S. Dhanoa et al. Patent US 7,030,240 B2], which acts as a potent and selective antagonist at the serotonin 5-HT2B receptor, with a 5-HT2Bbinding affinity (Ki) of 3.4nM, and high selectivity over the closely related 5-HT2A and 5-HT2C receptors and other receptor targets. PRX-08066 and other selective 5-HT2B antagonists are being researched for the treatment of pulmonary arterial hypertension, following the discovery that the potent 5-HT2B agonist norfenfluramine produces pulmonary arterial hypertension and subsequent heart valve damage. In animal studies, PRX-08066 has been found to reduce several key indicators of pulmonary arterial hypertension and improved cardiac output, with similar efficacy to established drugs for this condition such as bosentan, sildenafil, beraprost and iloprost. It is also being researched for potential anti-cancer applications, due to its ability to inhibit fibroblast activation.
Nelotanserin is a drug developed by Arena Pharmaceuticals which acts as an inverse agonist on the serotonin receptor subtype 5-HT2A and was under development for the treatment of insomnia. It was shown to be effective and well tolerated in clinical trials, but development was halted in December 2008 because the substance did not meet the trial's effectiveness endpoints. Research continues on newer analogues which may potentially be more successful. More recently, nelotanserin has been repurposed for the treatment of Lewy body disease. As of 2017, it is in phase II clinical trials for this indication.
PRX-03140 is a partial agonist (18% relative to 5-HT) of the 5-HT4 receptor that is being developed by EPIX Pharmaceuticals for Alzheimer's disease.
Levofenfluramine (INN), or (−)-3-trifluoromethyl-N-ethylamphetamine, also known as (−)-fenfluramine or (R)-fenfluramine, is a drug of the amphetamine family that, itself, was never marketed. It is the levorotatory enantiomer of fenfluramine, the racemic form of the compound, whereas the dextrorotatory enantiomer is dexfenfluramine. Both fenfluramine and dexfenfluramine are anorectic agents that have been used clinically in the treatment of obesity. However, they have since been discontinued due to reports of causing cardiovascular conditions such as valvular heart disease and pulmonary hypertension, adverse effects that are likely to be caused by excessive stimulation of 5-HT2B receptors expressed on heart valves.
Piromelatine (Neu-P11) is a multimodal sleep drug under development by Neurim Pharmaceuticals. It is an agonist at melatonin MT1/MT2 and serotonin 5-HT1A/5-HT1D receptors. Neurim is conducting a phase II randomized, placebo controlled trial of cognitive and sleep effects in Alzheimer's disease.
AVN-211 (CD-008-0173) is a drug which acts as a highly selective 5-HT6 receptor antagonist and is under development by Avineuro Pharmaceuticals for the treatment of schizophrenia. In early 2011, it successfully completed phase IIa clinical trials, with benefits on positive symptoms and some procognitive effects observed, and in mid 2013, phase IIb clinical trials for schizophrenia began. Avineuro Pharmaceuticals has also expressed intention to start clinical trials of AVN-211 for Alzheimer's disease in 2015.
Brilaroxazine, also known by the developmental code names RP-5063 and RP-5000, is an investigational atypical antipsychotic which is under development by Reviva Pharmaceuticals for the treatment of schizophrenia and schizoaffective disorder. Reviva Pharmaceuticals also intends to investigate brilaroxazine for the treatment of bipolar disorder, major depressive disorder, psychosis/agitation associated with Alzheimer's disease, Parkinson's disease psychosis, attention deficit hyperactivity disorder (ADD/ADHD), and autism. As of May 2015, it is in phase III clinical trials for schizophrenia.
AVN-101, a close structural analogue of latrepirdine, is a selective 5-HT6 receptor antagonist which is under development by Avineuro Pharmaceuticals for the treatment of Alzheimer's disease and anxiety disorders. As of November 2013, it is in phase II clinical trials for these indications.
