chemistry

Ritanserin

Ritanserin is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Ritanserin rather than just read about it. In short: Ritanserin, also known by its developmental code name R-55667, is a serotonin receptor antagonist which was under development for the treatment of anxiety disorders and major depressive disorder but was never marketed. It was also investigated for treatment of insomnia, especially to enhance sleep quality by significantly increasing slow wave sleep by virtue of potent and concomitant serotonin 5-HT2A and 5-HT2C rece…

Key takeaways

Ritanserin belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Ritanserin to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Ritanserin from memory before moving on to harder problems.

Reference excerpt

Ritanserin, also known by its developmental code name R-55667, is a serotonin receptor antagonist which was under development for the treatment of anxiety disorders and major depressive disorder but was never marketed. It was also investigated for treatment of insomnia, especially to enhance sleep quality by significantly increasing slow wave sleep by virtue of potent and concomitant serotonin 5-HT2A and 5-HT2C receptor antagonism. The drug is taken orally.

Pharmacology

Pharmacodynamics Ritanserin acts as a selective 5-HT2A (Ki = 0.45 nM) and 5-HT2C receptor (Ki = 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-HT2A, respectively). The affinity of ritanserin for the 5-HT1A receptor is less than 1 μM. In addition to its affinity for the 5-HT2A and 5-HT2C receptors, ritanserin also binds to and antagonizes the 5-HT1D, 5-HT2B, 5-HT5A, 5-HT6, and 5-HT7 receptors. Ritanserin blocks c-RAF activation and induces apoptotic cell death of non–small cell lung cancer and small cell lung cancer cells.

Pharmacokinetics The time to peak levels of ritanserin is 1.7 hours. Its elimination half-life is 54 hours.

Chemistry

Synthesis

Aminothiazole (2-thiazolamine) (1) is condensed with 2-acetylbutyrolactone [517-23-7] (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-[1,3]thiazolo[3,2-a]pyrimidin-5-one, CID:82612453 (4). Halogenation of the terminal alcohol with phosphorus oxychloride then yields 6-(2-chloroethyl)- 7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, [86488-00-8] (5). Alkylation with 4-(bis(4-fluorophenyl)methylene)piperidine, [58113-36-3] (6) would complete the synthesis of ritanserin (7).

History The atypical antipsychotic risperidone was developed via structural modification of ritanserin.

Society and culture

Names Ritanserin is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and BANTooltip British Approved Name. 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, schizophrenia, and migraine. It was also found to improve sleep in human volunteers. It reached phase 3 clinical trials for major depressive disorder prior to the discontinuation of its development. Some of the safety liabilities that led to its discontinuation of ritanserin for treatment of insomnia have led to its potential repurposing in the field of oncology. Specifically, it acts as a potent inhibitor of diacylglycerol kinase alpha (DGKα). As such, it may be used to treat certain types of glioblastoma and melanoma. It has also been used as a reference compound to identify putatively more selective and potent DGKα inhibitors to treat these forms of cancer as well as possibly others.

See also Serotonin 5-HT2A receptor antagonist Ketanserin Setoperone

References

Illustrations

Worked examples

Example 1 — a first encounter with Ritanserin

Start with the simplest possible case. Write down what Ritanserin claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Ritanserin before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Ritanserin ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Ritanserin

In research: Ritanserin appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Ritanserin in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Ritanserin is common in secondary-school and first-year university syllabi. It links to neighbouring topics 4-Fluorophenyl compounds, 5-HT2A antagonists, 5-HT2C antagonists, so understanding it makes those chapters shorter.
In everyday life: Look for Ritanserin outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Ritanserin in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Ritanserin means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Ritanserin out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Ritanserin in simple terms?

Why does Ritanserin matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Ritanserin?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Ritanserin.