<p><a href="https://www.bocsci.com/product/sb-243213-cas-200940-22-3-380839.html" rel="nofollow noreferrer">SB 243213</a> is an active, selective and high-affinity 5-HT2C receptor antagonist. It has improved anxiolytic profile and has the potential for schizophrenia and motor disorders.</p>

CC BY-SA 4.0
2023-06-05T11:00:11.290Z
Welcome and thanks for including your source of information. We encourage answers with some more background, though. In addition, copy-paste answers are frowned upon and in this case it doesn't make much sense either; *It has improved anxiolytic profile ...'* compared to... what?
AliceD
CC BY-SA 4.0
2023-06-05T07:14:41.423Z
2023-06-05T07:14:41.423Z
krystal
<p><a href="https://en.wikipedia.org/wiki/SB-243213" rel="nofollow noreferrer">SB-243213</a> acts as a selective inverse agonist for the 5-HT2C receptor.</p>

<p><a href="https://en.wikipedia.org/wiki/5-HT2C_receptor" rel="nofollow noreferrer">The 5-HT2C receptor</a> is one of many 5-HT receptors which are receptors that bind serotonin, and seems to play a major role in both suicide (<a href="https://www.nature.com/articles/1395631" rel="nofollow noreferrer">some suicide victims have an abnormally high number of 5-HT2C receptors in the prefrontal cortex</a>) and schizophrenia (<a href="https://www.ncbi.nlm.nih.gov/pubmed/28294132" rel="nofollow noreferrer">activation of 5-HT2C receptors reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action)</a>).</p>

<p>Chemicals which are commonly prescribed for major depressive disorder and schizophrenia are non-selective and affect a broad range of molecular targets (including other families of 5-HT2 receptors, and other targets) at varying binding affinities, while also producing a wide range of side effects related to those various molecular targets.</p>

<p>SB-243213 has better than 100x selectivity for 5-HT2C over all other receptor subtypes tested, and a longer duration of action compared to older 5-HT2C antagonist ligands.</p>

<p>It seems like a promising target for future research, but I can't find an example of it being tested in humans, but it seems to have had a <a href="https://www.ncbi.nlm.nih.gov/pubmed/11489455" rel="nofollow noreferrer">healthy anxiolytic response in rats</a> and a <a href="https://www.ncbi.nlm.nih.gov/pubmed/11888551" rel="nofollow noreferrer">significantly beneficial response on the rat sleep profile</a>, although this research is from almost 20 years ago.</p>

<p>Aside from distribution differences of 5-HT2C receptors in rat and human brains, what other differences could cause unexpected results and possible side effects if tested in a human?</p>

<p>One of the studies notes that positive results were seen at "10 mg/kg po" in rats, and having read the full text of one of the studies many tests were done with doses ranging from 1mg/kg to 10mg/kg, with tolerance studies up to 40mg/kg. Also, <a href="https://www.medchemexpress.com/HandlingInstruction/Compound%20Handling%20Instructions.pdf" rel="nofollow noreferrer">example routes and volumes for different animals are noted here</a>.</p>

<p>How can an appropriate, initial test dosage be calculated for humans? The <a href="https://documents.tocris.com/pdfs/tocris_msds/3527_sds.pdf" rel="nofollow noreferrer">SDS from a manufacturer</a> lists "<em>Acute Toxicity: IPR-RAT TDLo: 0.63mg/kg</em>". For a 250g rat, would that be ~15mg? For an 80kg human, would that be ~50g?</p>

<p>In what way would such a chemical be toxic? To the liver?</p>

<p><strong>What can happen if a human takes such a dose of SB-243213?</strong></p>

<p>If it hasn't been through a clinical trial, what are some of the risks?</p>

<p>From one of the articles above:</p>

<blockquote>
  <p>We have previously described the development of selective 5-HT2C receptor antagonists including SB-206553 and SB-242084...we have demonstrated an involvement of the 5-HT2C receptor in animal models of anxiety and depression and shown that such compounds do not possess either pro-convulsant or hyperphagic properties...Unfortunately these compounds were not suitable for progression into man for a number of reasons, including an interaction with cytochrome P450 enzymes. We have therefore developed SB-243213 as a selective 5-HT2C receptor antagonist (Bromidge et al., 2000) which does not interact with cytochrome P450 enzymes <strong>at concentrations up to 10uM</strong>. SB-243213 is currently in clinical development with potential for the treatment of a range of psychiatric diseases including anxiety, depression, and schizophrenia.</p>
</blockquote>

<p>Essentially I'm looking for reasons why this might not be suitable for humans, or examples of possible side effects.</p>

<p><strong>Why has this 20-year-old, apparently promising drug not proceeded beyond the clinical development mentioned?</strong></p>

<p>There are 18 articles mentioning "SB-243213" on DeepDyve. I'll continue to update this post as I find more information. After reading all of the articles I plan to contact some of the authors if I can't find an answer this question by myself.</p>

CC BY-SA 4.0
2020-01-20T14:16:15.617Z
Welcome to Psychology & Neuroscience SE! _"I'll continue to update this post as I find more information"_ Note that you are also allowed (and encouraged!) to answer your own question. At some point 'additional information' can form a (at least partial) answer. Thank you for a well-researched question!
Steven Jeuris
CC BY-SA 4.0
2020-01-30T20:52:35.910Z
Incredibly high selectivity might not be the best thing in a medication due to potential dosing errors. See fentanyl and its "super" derivatives... There is such a thing as [serotonin syndrome](https://en.wikipedia.org/wiki/Serotonin_syndrome) (e.g. overdosing with SSRI).
got trolled too much this week
<depression><psychopharmacology><schizophrenia><neuro-transmitters><serotonin>
What can happen if a human takes SB-243213?
SB-243213fan
# What can happen if a human takes SB-243213?

(Asked by: username_0 on 2020-01-19)

[SB-243213](https://en.wikipedia.org/wiki/SB-243213) acts as a selective inverse agonist for the 5-HT2C receptor.

[The 5-HT2C receptor](https://en.wikipedia.org/wiki/5-HT2C_receptor) is one of many 5-HT receptors which are receptors that bind serotonin, and seems to play a major role in both suicide ([some suicide victims have an abnormally high number of 5-HT2C receptors in the prefrontal cortex](https://www.nature.com/articles/1395631)) and schizophrenia ([activation of 5-HT2C receptors reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action)](https://www.ncbi.nlm.nih.gov/pubmed/28294132)).

Chemicals which are commonly prescribed for major depressive disorder and schizophrenia are non-selective and affect a broad range of molecular targets (including other families of 5-HT2 receptors, and other targets) at varying binding affinities, while also producing a wide range of side effects related to those various molecular targets.

SB-243213 has better than 100x selectivity for 5-HT2C over all other receptor subtypes tested, and a longer duration of action compared to older 5-HT2C antagonist ligands.

It seems like a promising target for future research, but I can't find an example of it being tested in humans, but it seems to have had a [healthy anxiolytic response in rats](https://www.ncbi.nlm.nih.gov/pubmed/11489455) and a [significantly beneficial response on the rat sleep profile](https://www.ncbi.nlm.nih.gov/pubmed/11888551), although this research is from almost 20 years ago.

Aside from distribution differences of 5-HT2C receptors in rat and human brains, what other differences could cause unexpected results and possible side effects if tested in a human?

One of the studies notes that positive results were seen at "10 mg/kg po" in rats, and having read the full text of one of the studies many tests were done with doses ranging from 1mg/kg to 10mg/kg, with tolerance studies up to 40mg/kg. Also, [example routes and volumes for different animals are noted here](https://www.medchemexpress.com/HandlingInstruction/Compound%20Handling%20Instructions.pdf).

How can an appropriate, initial test dosage be calculated for humans? The [SDS from a manufacturer](https://documents.tocris.com/pdfs/tocris_msds/3527_sds.pdf) lists "*Acute Toxicity: IPR-RAT TDLo: 0.63mg/kg*". For a 250g rat, would that be ~15mg? For an 80kg human, would that be ~50g?

In what way would such a chemical be toxic? To the liver?

**What can happen if a human takes such a dose of SB-243213?**

If it hasn't been through a clinical trial, what are some of the risks?

From one of the articles above:

> We have previously described the development of selective 5-HT2C receptor antagonists including SB-206553 and SB-242084...we have demonstrated an involvement of the 5-HT2C receptor in animal models of anxiety and depression and shown that such compounds do not possess either pro-convulsant or hyperphagic properties...Unfortunately these compounds were not suitable for progression into man for a number of reasons, including an interaction with cytochrome P450 enzymes. We have therefore developed SB-243213 as a selective 5-HT2C receptor antagonist (Bromidge et al., 2000) which does not interact with cytochrome P450 enzymes **at concentrations up to 10uM**. SB-243213 is currently in clinical development with potential for the treatment of a range of psychiatric diseases including anxiety, depression, and schizophrenia.

Essentially I'm looking for reasons why this might not be suitable for humans, or examples of possible side effects.

**Why has this 20-year-old, apparently promising drug not proceeded beyond the clinical development mentioned?**

There are 18 articles mentioning "SB-243213" on DeepDyve. I'll continue to update this post as I find more information. After reading all of the articles I plan to contact some of the authors if I can't find an answer this question by myself.

**Tags:** depression, psychopharmacology, schizophrenia, neuro-transmitters, serotonin

> **Comments:**
> **username_1**: Welcome to Psychology & Neuroscience SE! _"I'll continue to update this post as I find more information"_ Note that you are also allowed (and encouraged!) to answer your own question. At some point 'additional information' can form a (at least partial) answer. Thank you for a well-researched question!  
> **username_2**: Incredibly high selectivity might not be the best thing in a medication due to potential dosing errors. See fentanyl and its "super" derivatives... There is such a thing as [serotonin syndrome](https://en.wikipedia.org/wiki/Serotonin_syndrome) (e.g. overdosing with SSRI).  

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## 1 answers

### Answer by username_3 on 2023-06-05. Score: -1

[SB 243213](https://www.bocsci.com/product/sb-243213-cas-200940-22-3-380839.html) is an active, selective and high-affinity 5-HT2C receptor antagonist. It has improved anxiolytic profile and has the potential for schizophrenia and motor disorders.

> **Comments:**
> **username_4**: Welcome and thanks for including your source of information. We encourage answers with some more background, though. In addition, copy-paste answers are frowned upon and in this case it doesn't make much sense either; *It has improved anxiolytic profile ...'* compared to... what?  

---

