Ritanserin, also known by its developmental code name R-55667, is a

serotonin antagonist A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action at serotonin (5-HT) receptors. Types 5-HT2A antagonists Antagonists of the 5-HT2A receptor are sometimes used as atypical antipsychotics (contrast wi ...

medication described as an

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

, antidepressant, antiparkinsonian agent, and antihypertensive agent. It was never marketed for medical use due to

safety Safety is the state of being "safe", the condition of being protected from harm or other danger. Safety can also refer to the control of recognized hazards in order to achieve an acceptable level of risk. Meanings There are two slightly dif ...

problems but has been used in

scientific research The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...

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

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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 Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection (subcutaneous or intramuscular). The injectable versions ...

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 and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

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 wit ...

, and migraine. It was also found to improve

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

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