Ritanserin, also known by its developmental code name R-55667, is a serotonin antagonist medication described as an anxiolytic, antidepressant,

antiparkinsonian agent In the management of Parkinson's disease, due to the chronic nature of Parkinson's disease (PD), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutri ...

, and antihypertensive agent. It was never marketed for medical use due to safety problems but has been used in

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to study the serotonin system.

Pharmacology

Pharmacodynamics

Ritanserin acts as a selective 5-HT_2A (K_i = 0.45 nM) and 5-HT_2C receptor (K_i = 0.71 nM) antagonist. It has relatively low affinity for the H₁, D₂, α₁-adrenergic, and α₂-adrenergic receptors (39-, 77-, 107-, and 166-fold lower relative to 5-HT_2A, respectively). The affinity of ritanserin for the 5-HT_1A receptor is less than 1 μM. In addition to its affinity for the 5-HT_2A and 5-HT_2C receptors, ritanserin also binds to and antagonizes the 5-HT_1D, 5-HT_2B, 5-HT_5A, 5-HT₆, and 5-HT₇ receptors.

History

The

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...

risperidone was developed from ritanserin.

Society and culture

Names

''Ritanserin'' is the generic name of the drug and its , , and . It is also known by its developmental code name ''R-55667''.

Availability

Ritanserin was never approved or marketed for medical use.

Research

Ritanserin was tested in clinical trials for depression,

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil Turmoil may refer to: * ''Turmoil'' (1984 video game), a 1984 video game released by Bug-Byte * ''Turmoil'' (2016 video game), a 2016 indie oil tycoon video ...

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wi ...

, and

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. It was also found to improve

sleep Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited Perception, sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefuln ...

in human volunteers.

Synthesis

Aminothiazole (2-thiazolamine) (1) is condensed with 2-acetylbutyrolactone 17-23-7(2) under DS-trap until the water has separated. Condensation of this β-keto lactone can be visualized to involve initial attack on the reactive butyrolactone by the primary nitrogen; cyclodehydration of that hypothetical intermediate 3 gives 6-(2-hydroxyethyl)-7-methyl- ,3hiazolo

,2-a The comma is a punctuation mark that appears in several variants in different languages. It has the same shape as an apostrophe or single closing quotation mark () in many typefaces, but it differs from them in being placed on the baseline o ...

yrimidin-5-one
CID:82612453
(4). Halogenation of the terminal alcohol with phosphorus oxychloride then yields 6-(2-chloroethyl)- 7-methyl-5H-thiazolo

yrimidin-5-one, 6488-00-8(5). Alkylation with 4-(bis(4-fluorophenyl)methylene)piperidine, 8113-36-3(6) would complete the synthesis of ritanserin (7).

References

{{Serotonin receptor modulators 5-HT2A antagonists 5-HT2C antagonists Abandoned drugs CYP2D6 inhibitors Lactams Fluoroarenes Piperidines Thiazolopyrimidines