A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s). The ubiquitous presence of this enzyme means that non-specific inhibitors have a wide range of actions, the actions in the heart, and lungs being some of the first to find a therapeutic use.
Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.
Amisulpride, sold under the brand names Solian and Barhemsys, is a medication used in the treatment of schizophrenia, acute psychotic episodes, depression, and nausea and vomiting. It is specifically used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; at low doses by mouth to treat depression; and at higher doses by mouth to treat psychosis.
Rolipram is a selective phosphodiesterase-4 inhibitor discovered and developed by Schering AG as a potential antidepressant drug in the early 1990s. It served as a prototype molecule for several companies' drug discovery and development efforts. Rolipram was discontinued after clinical trials showed that its therapeutic window was too narrow; it could not be dosed at high enough levels to be effective without causing significant gastrointestinal side effects.
Molindone, sold under the brand name Moban, is an antipsychotic medication which is used in the United States in the treatment of schizophrenia. It is taken by mouth.
cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene.
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the PDE10A gene.
Xanomeline is a small molecule muscarinic acetylcholine receptor agonist that was first synthesized in a collaboration between Eli Lilly and Novo Nordisk as an investigational therapeutic being studied for the treatment of central nervous system (CNS) disorders.
Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.
Lurasidone, sold under the brand name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.
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.
Nepicastat is an inhibitor of dopamine β-hydroxylase (DBH), an enzyme that catalyzes the conversion of dopamine to norepinephrine.
Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and duration of action of acetylcholine in the central nervous system, autonomic ganglia and neuromuscular junctions, which are rich in acetylcholine receptors. Acetylcholinesterase inhibitors are one of two types of cholinesterase inhibitors; the other being butyryl-cholinesterase inhibitors. Acetylcholinesterase is the primary member of the cholinesterase enzyme family.
The plasma membrane monoamine transporter (PMAT) is a low-affinity monoamine transporter protein which in humans is encoded by the SLC29A4 gene. It is known alternatively as the human equilibrative nucleoside transporter-4 (hENT4). It was discovered in 2004 and has been identified as a potential alternate target for treating various conditions.
Ecopipam is a dopamine antagonist which is under development for the treatment of Lesch-Nyhan syndrome, Tourette syndrome, speech disorders, and restless legs syndrome. It is taken by mouth.
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.
Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic medication used for the treatment of major depressive disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease.
Evenamide is a selective voltage-gated sodium channel blocker, including subtypes Nav1.3, Nav1.7, and Nav1.8, which is described as an antipsychotic and is under development by Newron Pharmaceuticals as an add-on therapy for the treatment of schizophrenia. The drug has shown efficacy in animal models of psychosis, mania, depression, and aggression. It has completed phase I clinical trials, and phase II clinical trials will be commenced in the third quarter of 2015.
MK-8189 is a selective phosphodiesterase 10A inhibitor being developed for schizophrenia. It is developed by Merck in collaboration with Royalty Pharma.
The conditioned avoidance response (CAR) test, also known as the active avoidance test, is an animal test used to identify drugs with antipsychotic-like effects. It is most commonly employed as a two-way active avoidance test with rodents. The test assesses the conditioned ability of an animal to avoid an unpleasant stimulus. Drugs that selectively suppress conditioned avoidance responses without affecting escape behavior are considered to have antipsychotic-like activity. Variations of the test, like testing for enhancement of avoidance and escape responses, have also been used to assess other drug effects, like pro-motivational and antidepressant-like effects.
