 | |
| Legal status | |
|---|---|
| Legal status |
|
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| Chemical and physical data | |
| Formula | C19H22N6OS |
| Molar mass | 382.49 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
MK-8189 is a selective phosphodiesterase 10A inhibitor being developed for schizophrenia. It is developed by Merck in collaboration with Royalty Pharma. [1] [2] [3] [4]
Fluvoxamine, commonly sold under the brand names Luvox and Faverin, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and obsessive–compulsive disorder (OCD), but is also used to treat anxiety disorders such as panic disorder, social anxiety disorder, and post-traumatic stress disorder.
Sarcosine, also known as N-methylglycine, or monomethylglycine, is a amino acid with the formula CH3N(H)CH2CO2H. It exists at neutral pH as the zwitterion CH3N+(H)2CH2CO2−, which can be obtained as a white, water-soluble powder. Like some amino acids, sarcosine converts to a cation at low pH and an anion at high pH, with the respective formulas CH3N+(H)2CH2CO2H and CH3N(H)CH2CO2−. Sarcosine is a close relative of glycine, with a secondary amine in place of the primary amine.
Mirtazapine, sold under the brand name Remeron amongst others, is an atypical tetracyclic antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks, but can also manifest as early as one to two weeks. It is often used in cases of depression complicated by anxiety or insomnia. The effectiveness of mirtazapine is comparable to other commonly prescribed antidepressants. It is taken by mouth.
Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines, catecholestrogens, and various drugs and substances having a catechol structure. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene. Two isoforms of COMT are produced: the soluble short form (S-COMT) and the membrane bound long form (MB-COMT). As the regulation of catecholamines is impaired in a number of medical conditions, several pharmaceutical drugs target COMT to alter its activity and therefore the availability of catecholamines. COMT was first discovered by the biochemist Julius Axelrod in 1957.
Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
Dizocilpine (INN), also known as MK-801, is a pore blocker of the N-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is normally blocked with a magnesium ion and requires depolarization of the neuron to remove the magnesium and allow the glutamate to open the channel, causing an influx of calcium, which then leads to subsequent depolarization. Dizocilpine binds inside the ion channel of the receptor at several of PCP's binding sites thus preventing the flow of ions, including calcium (Ca2+), through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug acts as a potent anti-convulsant and probably has dissociative anesthetic properties, but it is not used clinically for this purpose because of the discovery of brain lesions, called Olney's lesions (see below), in laboratory rats. Dizocilpine is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It inhibits the induction of long term potentiation and has been found to impair the acquisition of difficult, but not easy, learning tasks in rats and primates. Because of these effects of dizocilpine, the NMDA receptor pore blocker ketamine is used instead as a dissociative anesthetic in human medical procedures. While ketamine may also trigger temporary psychosis in certain individuals, its short half-life and lower potency make it a much safer clinical option. However, dizocilpine is the most frequently used uncompetitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.
Biological psychiatry or biopsychiatry is an approach to psychiatry that aims to understand mental disorder in terms of the biological function of the nervous system. It is interdisciplinary in its approach and draws on sciences such as neuroscience, psychopharmacology, biochemistry, genetics, epigenetics and physiology to investigate the biological bases of behavior and psychopathology. Biopsychiatry is the branch of medicine which deals with the study of the biological function of the nervous system in mental disorders.
The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the DRD4 gene on chromosome 11 at 11p15.5.
Radafaxine (developmental code name GW-353,162), also known as (2S,3S)-hydroxybupropion or (S,S)-hydroxybupropion, is a norepinephrine–dopamine reuptake inhibitor (NDRI) which was under development by GlaxoSmithKline in the 2000s for a variety of different indications but was never marketed. These uses included treatment of restless legs syndrome, major depressive disorder, bipolar disorder, neuropathic pain, fibromyalgia, and obesity. Regulatory filing was planned for 2007, but development was discontinued in 2006 due to "poor test results".
Benzofuranylpropylaminopentane is a drug with an unusual monoamine-release potentiating mechanism of action. It can loosely be grouped with the stimulant or antidepressant drug families, but its mechanism of action is quite different.
Metabotropic glutamate receptor 3 (mGluR3) is an inhibitory Gi/G0-coupled G-protein coupled receptor (GPCR) generally localized to presynaptic sites of neurons in classical circuits. However, in higher cortical circuits in primates, mGluR3 are localized post-synaptically, where they strengthen rather than weaken synaptic connectivity. In humans, mGluR3 is encoded by the GRM3 gene. Deficits in mGluR3 signaling have been linked to impaired cognition in humans, and to increased risk of schizophrenia, consistent with their expanding role in cortical evolution.
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the PDE10A gene.
Altropane is a phenyltropane derivative which acts as a potent dopamine reuptake inhibitor and long-acting stimulant drug. It has mainly been used as the 125I radiolabelled form for mapping the distribution of dopamine transporters in the brain, and consequently this has led to its development as a potential diagnostic tool for early detection of Parkinson's disease. It is also being investigated for potential use in the diagnosis and treatment of attention deficit hyperactivity disorder (ADHD).
Mardepodect is a drug which was developed by Pfizer for the treatment of schizophrenia. It acts as a phosphodiesterase inhibitor selective for the PDE10A subtype. The PDE10A enzyme is expressed primarily in the brain, mostly in the striatum, nucleus accumbens and olfactory tubercle, and is thought to be particularly important in regulating the activity of dopamine-sensitive medium spiny neurons in the striatum which are known to be targets of conventional antipsychotic drugs. Older PDE10A inhibitors such as papaverine have been shown to produce antipsychotic effects in animal models, and more potent and selective PDE10A inhibitors are a current area of research for novel antipsychotic drugs which act through a different pathway to conventional dopamine or 5-HT2A antagonist drugs and may have a more favourable side effects profile. Mardepodect is currently one of the furthest advanced PDE10A inhibitors in development and has progressed through to Phase II clinical trials in humans. In 2017, development of mardepodect for the treatment of schizophrenia and Huntington's disease was discontinued.
CDPPB is a drug used in scientific research which acts as a positive allosteric modulator selective for the metabotropic glutamate receptor subtype mGluR5. It has antipsychotic effects in animal models, and mGluR5 modulators are under investigation as potential drugs for the treatment of schizophrenia, as well as other applications.
SSR180711 is a drug that acts as a potent and selective partial agonist for the α7 subtype of neural nicotinic acetylcholine receptors. In animal studies, it shows nootropic effects and may be useful in the treatment of schizophrenia.
A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibitors. The PDE4 family of enzymes are the most prevalent PDE in immune cells. They are predominantly responsible for hydrolyzing cAMP within both immune cells and cells in the central nervous system.
Sonepiprazole (U-101,387, PNU-101,387-G) is a drug of the phenylpiperazine class which acts as a highly selective D4 receptor antagonist. In animals, unlike D2 receptor antagonists like haloperidol, sonepiprazole does not block the behavioral effects of amphetamine or apomorphine, does not alter spontaneous locomotor activity on its own, and lacks extrapyramidal and neuroendocrine effects. However, it does reverse the prepulse inhibition deficits induced by apomorphine, and has also been shown to enhance cortical activity and inhibit stress-induced cognitive impairment. As a result, it was investigated as an antipsychotic for the treatment of schizophrenia in a placebo-controlled clinical trial, but in contrast to its comparator olanzapine no benefits were found and it was not researched further for this indication.
AM-630 (6-Iodopravadoline) is a drug that acts as a potent and selective inverse agonist for the cannabinoid receptor CB2, with a Ki of 32.1 nM at CB2 and 165x selectivity over CB1, at which it acted as a weak partial agonist. It is used in the study of CB2 mediated responses and has been used to investigate the possible role of CB2 receptors in the brain. AM-630 is significant as one of the first indole derived cannabinoid ligands substituted on the 6-position of the indole ring, a position that has subsequently been found to be important in determining affinity and efficacy at both the CB1 and CB2 receptors, and has led to the development of many related derivatives.
BI 1569912 is a selective modulator of the NMDA receptor. It is being developed by Boehringer Ingelheim to treat major depressive disorder. As of 2023, it is in a Phase I trial.