Asenapine
Encyclopedia
Asenapine is a new atypical antipsychotic
developed for the treatment of schizophrenia
and acute mania associated with bipolar disorder
by Schering-Plough
after its November 19, 2007 merger with Organon International
. Development of the drug, through Phase III trials, began while Organon was still a part of Akzo Nobel
. Preliminary data indicate that it has minimal anticholinergic and cardiovascular side effects, as well as minimal weight gain. Over 3000 patients have participated in clinical trial
s of asenapine, and the FDA
accepted the manufacturer's NDA
on November 26, 2007 for standard review.
Some American psychiatrists have begun to prescribe the drug to combat veterans with severe PTSD nightmares as an "off-label" use, although this use is not yet allowed by the United States Department of Veterans Administration. (Search "Formulary" at www.va.gov)
, including the serotonin
5-HT1A (8.6), 5-HT1B (8.4), 5-HT2A (10.2), 5-HT2B
(9.8), 5-HT2C (10.5), 5-HT5A (8.8), 5-HT6 (9.5), and 5-HT7 (9.9) receptors, the adrenergic α1
(8.9), α2A
(8.9), α2B
(9.5), and α2C
(8.9) receptors, the dopamine
D1
(8.9), D2
(8.9), D3
(9.4), and D4 (9.0) receptors, and the histamine
H1 (9.0) and H2 (8.2) receptors. It has much lower affinity (pKi < 5) for the muscarinic acetylcholine receptor
s. Asenapine behaves as an a partial agonist
at the 5-HT1A and D1 receptors. At all other targets Asenapine is an antagonist
. As of November 2010 Asenapine is also in clinical trials at UC Irvine to treat stuttering.
and acute treatment of manic or mixed episodes associated with bipolar I
disorder with or without psychotic features in adults.
, oral hypoesthesia
, somnolence, dizziness, extrapyramidal symptoms other than akathisia, weight gain, insomnia, extreme sedation, headache.
Rare side effects: Neuroleptic malignant syndrome
(Combination of fever
, muscle stiffness, faster breathing
, sweating
, reduced consciousness, and sudden change in blood pressure
and heart rate
.), tardive dyskinesia.
The FDA has warned healthcare professionals and patients that serious allergic reactions have been reported with the use of Saphris.Healthcare professionals and patients are encouraged to report adverse events or side effects to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.
Reduction step is sodium in liquid ammonia.
Atypical antipsychotic
The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
developed for the treatment 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 acute mania associated with bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
by Schering-Plough
Schering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...
after its November 19, 2007 merger with Organon International
Organon International
Organon is a human pharmaceutical company headquartered in Oss, Netherlands. In November 2007 the company became a part of Schering-Plough Corporation, acquired Organon, active pharmaceutical ingredient producer Diosynth , and its veterinary pharmaceutical sister company Intervet from Akzo Nobel. ...
. Development of the drug, through Phase III trials, began while Organon was still a part of Akzo Nobel
Akzo Nobel
Akzo Nobel N.V., trading as AkzoNobel, is a Dutch multinational, active in the fields of decorative paints, performance coatings and specialty chemicals. Headquartered in Amsterdam, the company has activities in more than 80 countries, and employs approximately 55,000 people. Sales in 2010 were EUR...
. Preliminary data indicate that it has minimal anticholinergic and cardiovascular side effects, as well as minimal weight gain. Over 3000 patients have participated 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 of asenapine, and the FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
accepted the manufacturer's NDA
New drug application
The New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the Food and Drug Administration approve a new pharmaceutical for sale and marketing...
on November 26, 2007 for standard review.
Some American psychiatrists have begun to prescribe the drug to combat veterans with severe PTSD nightmares as an "off-label" use, although this use is not yet allowed by the United States Department of Veterans Administration. (Search "Formulary" at www.va.gov)
Pharmacology
Asenapine shows high affinity (pKi) for numerous receptorsReceptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
, including the serotonin
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...
5-HT1A (8.6), 5-HT1B (8.4), 5-HT2A (10.2), 5-HT2B
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:...
(9.8), 5-HT2C (10.5), 5-HT5A (8.8), 5-HT6 (9.5), and 5-HT7 (9.9) receptors, the adrenergic α1
Alpha-1 adrenergic receptor
The alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...
(8.9), α2A
Alpha-2A adrenergic receptor
The alpha-2A adrenergic receptor , also known as ADRA2A, is an alpha-2 adrenergic receptor, and also denotes the human gene encoding it.-Role in Central Nervous System:...
(8.9), α2B
Alpha-2B adrenergic receptor
The alpha-2B adrenergic receptor , is a G-protein coupled receptor. It is a subtype of the adrenergic receptor family. The human gene encoding this receptor has the symbol ADRA2B.ADRA2B orthologs have been identified in several mammals....
(9.5), and α2C
Alpha-2C adrenergic receptor
The alpha-2C adrenergic receptor , also known as ADRA2C, is an alpha-2 adrenergic receptor, and also denotes the human gene encoding it.-Agonists:* -3-Nitrobiphenyline -Antagonists:...
(8.9) receptors, the 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...
D1
Dopamine receptor D1
Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.- Function :This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G-protein-coupled receptor stimulates...
(8.9), D2
Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
(8.9), D3
Dopamine receptor D3
D dopamine receptor is a protein that in humans is encoded by the DRD3 gene.This gene encodes the D3 subtype of the dopamine receptor. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that...
(9.4), and D4 (9.0) receptors, and the histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
H1 (9.0) and H2 (8.2) receptors. It has much lower affinity (pKi < 5) for the muscarinic acetylcholine receptor
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
s. Asenapine behaves as an a partial agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
at the 5-HT1A and D1 receptors. At all other targets Asenapine is an 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...
. As of November 2010 Asenapine is also in clinical trials at UC Irvine to treat stuttering.
| Receptor Receptor (biochemistry) In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism... | Affinity (pKi) | Affinity (Ki (nM)) |
|---|---|---|
| 5-HT1A 5-HT1A receptor The 5-HT1A 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 Gi/Go and mediates inhibitory neurotransmission... |
8.6 | 2.5 |
| 5-HT1B 5-HT1B receptor 5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT1B receptor is a 5-HT receptor subtype.-Tissue distribution and function:... |
8.4 | 4.0 |
| 5-HT2A 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... |
10.2 | 0.06 |
| 5-HT2B 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:... |
9.8 | 0.16 |
| 5-HT2C 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... |
10.5 | 0.03 |
| 5-HT5A 5-HT5A receptor 5-hydroxytryptamine receptor 5A, also known as HTR5A, is a protein which in humans is encoded by the HTR5A gene.- Function :... |
8.8 | 1.6 |
| 5-HT6 5-HT6 receptor The 5-HT6 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 Gs/Go and mediates excitatory neurotransmission. HTR6 denotes the human gene encoding for the receptor.-Distribution:The 5-HT6 receptor is... |
9.5 | 0.25 |
| 5-HT7 5-HT7 receptor The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin The 5-HT7 receptor is coupled to Gs and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various... |
9.9 | 0.13 |
| α1-Adrenergic Alpha-1 adrenergic receptor The alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic... |
8.9 | 1.2 |
| α2A-Adrenergic Alpha-2A adrenergic receptor The alpha-2A adrenergic receptor , also known as ADRA2A, is an alpha-2 adrenergic receptor, and also denotes the human gene encoding it.-Role in Central Nervous System:... |
8.9 | 1.2 |
| α2B-Adrenergic Alpha-2B adrenergic receptor The alpha-2B adrenergic receptor , is a G-protein coupled receptor. It is a subtype of the adrenergic receptor family. The human gene encoding this receptor has the symbol ADRA2B.ADRA2B orthologs have been identified in several mammals.... |
9.5 | ? (~0.25) |
| α2C-Adrenergic Alpha-2C adrenergic receptor The alpha-2C adrenergic receptor , also known as ADRA2C, is an alpha-2 adrenergic receptor, and also denotes the human gene encoding it.-Agonists:* -3-Nitrobiphenyline -Antagonists:... |
8.9 | 1.2 |
| D1 | 8.9 | 1.4 |
| D2 | 8.9 | 1.3 |
| D3 | 9.4 | 0.42 |
| D4 | 9.0 | 1.1 |
| H1 H1 receptor The H1 receptor is a histamine receptor belonging to the family of Rhodopsin like G-protein-coupled receptors. This receptor, which is activated by the biogenic amine histamine, is expressed throughout the body, to be specific, in smooth muscles, on vascular endothelial cells, in the heart, and in... |
9.0 | 1.0 |
| H2 H2 receptor H2 receptors are positively coupled to adenylate cyclase via Gs. It is a potent stimulant of cAMP production. It increases the intracellular Ca2+ concentrations and release Ca2+ from intracellular stores... |
8.2 | 6.2 |
| mACh Muscarinic acetylcholine receptor Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells... |
< 5 | 8,128 |
Indications and usage
Asenapine has been approved by the FDA for the acute treatment of adults with schizophreniaSchizophrenia
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 acute treatment of manic or mixed episodes associated with bipolar I
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
disorder with or without psychotic features in adults.
Side effects
Common side effects: (incidence at least 5% or greater and at least twice that for placebo or greater than 10% regardless of placebo rate) Severe akathisiaAkathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
, oral hypoesthesia
Hypoesthesia
Hypoesthesia refers to a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli....
, somnolence, dizziness, extrapyramidal symptoms other than akathisia, weight gain, insomnia, extreme sedation, headache.
Rare side effects: Neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
(Combination of fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, muscle stiffness, faster breathing
Hyperventilation
Hyperventilation or overbreathing is the state of breathing faster or deeper than normal, causing excessive expulsion of circulating carbon dioxide. It can result from a psychological state such as a panic attack, from a physiological condition such as metabolic acidosis, can be brought about by...
, sweating
Sweating
Perspiration is the production of a fluid consisting primarily of water as well as various dissolved solids , that is excreted by the sweat glands in the skin of mammals...
, reduced consciousness, and sudden change in blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
and heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
.), tardive dyskinesia.
The FDA has warned healthcare professionals and patients that serious allergic reactions have been reported with the use of Saphris.Healthcare professionals and patients are encouraged to report adverse events or side effects to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.
Synthesis
J. van der Burg, .Reduction step is sodium in liquid ammonia.