Vabicaserin
Encyclopedia
Vabicaserin was a novel antipsychotic
and anorectic
under development by Wyeth
. As of 2010 it is no longer in clinical trial
s for the treatment of psychosis
. It was also under investigation as an antidepressant
but this indication appears to have been dropped as well.
Vabicaserin acts as a selective
5-HT2C receptor
full agonist (Ki = 3 nM; EC50 = 8 nM; IA = 100% (relative to 5-HT
)) and 5-HT2B receptor
antagonist
(IC50 = 29 nM). It is also a very weak antagonist at the 5-HT2A receptor
(IC50 = 1,650 nM), though this action is not clinically significant. By activating 5-HT2C receptors, vabicaserin inhibits dopamine
release in the mesolimbic pathway
, likely underlying its efficacy in alleviating positive symptoms of schizophrenia
, and increases acetylcholine
and glutamate levels in the prefrontal cortex
, suggesting benefits against cognitive symptoms as well.
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
and anorectic
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
under development by Wyeth
Wyeth
Wyeth, formerly one of the companies owned by American Home Products Corporation , was a pharmaceutical company. The company was based in Madison, New Jersey, USA...
. As of 2010 it is no longer in clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s for the treatment of psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
. It was also under investigation as an antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
but this indication appears to have been dropped as well.
Vabicaserin acts as a selective
Binding selectivity
Binding selectivity refers to the differing affinities with which different ligands bind to a substrate forming a complex. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate...
5-HT2C receptor
5-HT2C receptor
The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the...
full agonist (Ki = 3 nM; EC50 = 8 nM; IA = 100% (relative to 5-HT
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
)) and 5-HT2B receptor
5-HT2B receptor
5-hydroxytryptamine receptor 2B, also known as HTR2B, is a 5-HT2 receptor, but also denotes the human gene encoding it.-Function:...
antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
(IC50 = 29 nM). It is also a very weak antagonist at the 5-HT2A receptor
5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
(IC50 = 1,650 nM), though this action is not clinically significant. By activating 5-HT2C receptors, vabicaserin inhibits dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
release in the mesolimbic pathway
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...
, likely underlying its efficacy in alleviating positive symptoms of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, and increases acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
and glutamate levels in the prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
, suggesting benefits against cognitive symptoms as well.