Altanserin

Altanserin is a compound that binds to the 5-HT_2A receptor (5-Hydroxytryptamine ( serotonin) 2A receptor). 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 5-HT_2A neuroreceptors. Besides human neuroimaging studies altanserin has also been used in the study of rats.

An alternative for PET imaging the 5-HT_2A receptor is the
[ ¹¹C] volinanserin (MDL-100,907) radioligand.
¹⁸F-altanserin and ³H-volinanserin have shown very comparable binding.
Both altanserin and MDL 100,907 are 5-HT_2A receptor antagonists.
sup>18Fsetoperone can also be used in PET.

An alternative SPECT radioligand is the sup>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.

Human brain mapping studies with altanserin

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-HT_2A binding and the brain region is used as a reference in some studies, even though an autoradiography study has found nonnegligible levels of 5-HT_2A binding in the human cerebellum,
and another type of study have observed strong immunoreaction against 5-HT_2A receptor protein in rat Purkinje cells.

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-HT_2A 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-HT_2A 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".

Synthesis

The reaction of 4-(4-fluorobenzoyl)piperidine 6346-57-7(1) with 2-bromoethylamine 07-09-5gives -(2-aminoethyl)piperidin-4-yl(4-fluorophenyl)methanone 3763-22-8(2). The reaction of the terminal amino group with thiophosgene 63-71-8leads to the corresponding isothiocyanate derivative, 4-fluorophenyl 1-(2-isothiocyanatoethyl)piperidin-4-yl ketone 4946-22-5(3). Upon reaction of this reactive intermediate with ethyl anthranilate 7-25-2(4), the transient addition product might be expected to be initially formed (5'). An intramolecular lactamization to the heterocyclic ring then occurs giving altanserin (6).

See also

* Ketanserin
* Pirenperone
* Setoperone

References

{{Serotonin receptor modulators

5-HT2A antagonists
Fluoroarenes
Ketones
Lactams
PET radiotracers
Piperidines
Quinazolines
Thioureas