Altanserin
Encyclopedia
Altanserin is a compound that binds
to the 5-HT2A receptor
(serotonin
2A receptor).
It is a yellowish solid.
Labeled with the isotope
fluorine-18
it is used as a radioligand
in positron emission tomography
(PET) studies of the brain
, i.e., studies of the serotonin-2A neuroreceptors.
Besides human neuroimaging
studies altanserin has also been used in the study of rat
s.
An alternative for PET imaging the 5-HT2A receptor is the
[11C]MDL 100,907 radioligand.
Fluorine-18-altanserin and tritium
-MDL 100,907 have shown very comparable binding.
Both altanserin and MDL 100,907 are 5-HT2A receptor antagonist
s.
[18F]-setoperone
can also be used in PET.
An alternative SPECT radioligand is the [123I]-5-I-R91150
receptor antagonist.
A rapid chemical synthesis of fluorine-18 and H-2
dual-labeled altanserin has been described.
Other ligands for other parts of the serotonin system used in PET studies are, e.g., DASB
, ketanserin
and WAY-100635
.
altanserin is probably not used in clinical routine.
However, there have been performed several research-based neuroimaging
studies with the compound in humans since the 1990s.
Some of these studies have considered methodogical issues such as the reproducibility
of the method
or whether to use constant infusion or bolus-infusion delivery of altanserin.
Other studies have compared altanserin binding
to subject variables such as age
, personality trait and neuropsychiatric disorder.
The altanserin PET scan shows high binding in neocortex
.
The cerebellum
is often regarded as a region with no specific 5-HT2A binding and the brain region is used as a reference in some studies, even though an autoradiography study has found nonnegligible levels of 5-HT2A binding in the human cerebellum,
and another type of study have observed strong immunoreaction against 5-HT2A receptor protein in rat Purkinje cell
s.
In the table below is an overview of the results of altanserin binding seen in human PET-studies.
A consistent finding across altanserin studies has been that the binding decreases with age.
This is in line with in vitro
studies of the 5-HT2A receptor,
as well as PET studies with other radioligands that binds to the receptor.
The result for recovered bulimia-type anorexia nervosa
is in line with a SPECT study of anorexia nervosa patients, that found a decrease in frontal, occipital and parietal cortices.
The results of PET studies of the 5-HT2A in depression
has been mixed.
Altanserin binding has also been examine in twins
, where one study showed higher correlation between monozygotic twin pairs than between dizygotic twin pairs, giving evidence that the binding is "strongly genetically determined".
Binding (molecular)
Molecular binding is an attractive interaction between two molecules which results in a stable association in which the molecules are in close proximity to each other...
to 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...
(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...
2A receptor).
It is a yellowish solid.
Labeled with the isotope
Isotope
Isotopes are variants of atoms of a particular chemical element, which have differing numbers of neutrons. Atoms of a particular element by definition must contain the same number of protons but may have a distinct number of neutrons which differs from atom to atom, without changing the designation...
fluorine-18
Fluorine-18
Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....
it is used as a radioligand
Radioligand
A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....
in positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) studies of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, i.e., studies of the serotonin-2A neuroreceptors.
Besides human neuroimaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...
studies altanserin has also been used in the study of rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...
s.
An alternative for PET imaging the 5-HT2A receptor is the
[11C]MDL 100,907 radioligand.
Fluorine-18-altanserin and tritium
Tritium
Tritium is a radioactive isotope of hydrogen. The nucleus of tritium contains one proton and two neutrons, whereas the nucleus of protium contains one proton and no neutrons...
-MDL 100,907 have shown very comparable binding.
Both altanserin and MDL 100,907 are 5-HT2A receptor 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...
s.
[18F]-setoperone
Setoperone
Setoperone is a compound that is a ligand to the 5-HT2A receptor.It can be radiolabeled with the radioisotope fluorine-18 and used as a radioligand with positron emission tomography ....
can also be used in PET.
An alternative SPECT radioligand is the [123I]-5-I-R91150
5-I-R91150
5-I-R91150 is a compound that acts as a potent and selective antagonist of 5-HT2A receptors. Its main application is as its iodine-123 radiolabeled form, in which it can be used in SPECT scanning in human neuroimaging studies, to examine the distribution of the 5-HT2A receptor subtype in the...
receptor antagonist.
A rapid chemical synthesis of fluorine-18 and H-2
Deuterium
Deuterium, also called heavy hydrogen, is one of two stable isotopes of hydrogen. It has a natural abundance in Earth's oceans of about one atom in of hydrogen . Deuterium accounts for approximately 0.0156% of all naturally occurring hydrogen in Earth's oceans, while the most common isotope ...
dual-labeled altanserin has been described.
Other ligands for other parts of the serotonin system used in PET studies are, e.g., DASB
DASB
DASB is a compound that binds to the serotonin transporter.Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography since around year 2000....
, ketanserin
Ketanserin
Ketanserin is a drug with affinity for multiple G protein-coupled receptors . Initially it was believed to be a highly selective antagonist for serotonin 5-HT2A receptors, however this is not true. Ketanserin only has moderate selectivity for 5-HT2A receptors over 5-HT2C receptors...
and WAY-100635
WAY-100635
WAY-100,635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the D4 receptor. It is sometimes referred to as a silent...
.
Human brain mapping studies with altanserin
However, there have been performed several research-based neuroimaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...
studies with the compound in humans since the 1990s.
Some of these studies have considered methodogical issues such as the reproducibility
Reproducibility
Reproducibility is the ability of an experiment or study to be accurately reproduced, or replicated, by someone else working independently...
of the method
or whether to use constant infusion or bolus-infusion delivery of altanserin.
Other studies have compared altanserin binding
Binding (molecular)
Molecular binding is an attractive interaction between two molecules which results in a stable association in which the molecules are in close proximity to each other...
to subject variables such as age
Ageing
Ageing or aging is the accumulation of changes in a person over time. Ageing in humans refers to a multidimensional process of physical, psychological, and social change. Some dimensions of ageing grow and expand over time, while others decline...
, personality trait and neuropsychiatric disorder.
The altanserin PET scan shows high binding in neocortex
Neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
.
The cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
is often regarded as a region with no specific 5-HT2A binding and the brain region is used as a reference in some studies, even though an autoradiography study has found nonnegligible levels of 5-HT2A binding in the human cerebellum,
and another type of study have observed strong immunoreaction against 5-HT2A receptor protein in rat Purkinje cell
Purkinje cell
For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons , are a class of GABAergic neurons located in the cerebellar cortex...
s.
In the table below is an overview of the results of altanserin binding seen in human PET-studies.
A consistent finding across altanserin studies has been that the binding decreases with age.
This is in line with in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
studies of the 5-HT2A receptor,
as well as PET studies with other radioligands that binds to the receptor.
The result for recovered bulimia-type anorexia nervosa
Anorexia nervosa
Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...
is in line with a SPECT study of anorexia nervosa patients, that found a decrease in frontal, occipital and parietal cortices.
The results of PET studies of the 5-HT2A in depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
has been mixed.
Altanserin binding has also been examine in twins
TWINS
Two Wide-Angle Imaging Neutral-Atom Spectrometers are a pair of NASA instruments aboard two United States National Reconnaissance Office satellites in Molniya orbits. TWINS was designed to provide stereo images of the Earth's ring current. The first instrument, TWINS-1, was launched aboard USA-184...
, where one study showed higher correlation between monozygotic twin pairs than between dizygotic twin pairs, giving evidence that the binding is "strongly genetically determined".
| What | Result | Reference |
|---|---|---|
| Sex Sex In biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents... |
Higher binding in men | |
| Body mass index Body mass index The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing... |
Correlation in cortex | |
| Neuroticism Neuroticism Neuroticism is a fundamental personality trait in the study of psychology. It is an enduring tendency to experience negative emotional states. Individuals who score high on neuroticism are more likely than the average to experience such feelings as anxiety, anger, guilt, and depressed mood... (NEO PI-R) |
Increase in frontolimbic region | |
| Tourette syndrome Tourette syndrome Tourette syndrome is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple physical tics and at least one vocal tic; these tics characteristically wax and wane... |
Increase | |
| Obsessive-compulsive disorder Obsessive-compulsive disorder Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions... |
Increase in caudate nuclei Caudate nucleus The caudate nucleus is a nucleus located within the basal ganglia of the brains of many animal species. The caudate nucleus is an important part of the brain's learning and memory system.-Anatomy:... |
|
| (Recovered) bulimia-type anorexia nervosa Anorexia nervosa Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate... |
Decrease in left subgenual cingulate, left parietal cortex and right occipital cortex | |
| Unipolar depression | Decrease in a region in right hemisphere (posterolateral orbitofrontal cortex Orbitofrontal cortex The orbitofrontal cortex is a prefrontal cortex region in the frontal lobes in the brain which is involved in the cognitive processing of decision-making... and the anterior insular cortex Insular cortex In each hemisphere of the mammalian brain the insular cortex is a portion of the cerebral cortex folded deep within the lateral sulcus between the temporal lobe and the frontal lobe. The cortical area overlying it towards the lateral surface of the brain is the operculum... ) |
|
| Major depressive disorder | Decrease in hippocampus Hippocampus The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in... |
|
| Older depressed patients | Decrease in hippocampus Hippocampus The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in... |
|
| Borderline personality disorder Borderline personality disorder Borderline personality disorder is a personality disorder described as a prolonged disturbance of personality function in a person , characterized by depth and variability of moods.The disorder typically involves unusual levels of instability in mood; black and white thinking, or splitting; the... |
Increase in hippocampus Hippocampus The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in... |
|
| 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... |
No significant cortical difference, higher binding in caudate Caudate Caudate can refer to:* Caudate nucleus* Caudate lobe of liver* Cauda equina* Members of the Caudata order.... |
|
| At-risk mental state | Decrease | See also |
| Age | Decrease | |
| Age | Decrease | |
| Age | Decrease in cortical Cerebral cortex The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different... regions (except occipital), increase in cerebellum Cerebellum The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established... |
|
| Mild cognitive impairment Mild cognitive impairment Mild cognitive impairment is a brain-function syndrome involving the onset and evolution of cognitive impairments beyond those expected based on the age and education of the individual, but which are not significant enough to interfere with their daily activities... |
Decrease | |
| Alzheimer's disease Alzheimer's disease Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death... |
Decrease in amygdalo Amygdala The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-... -hippocampal Hippocampus The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in... complex and cortical regions, such as anterior cingulate, lateral temporal cortex, 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... and sensorimotor cortex |