A Selective Serotonin Antagonist Is A Potent Antidepressant

[haidut]

Fraud, fraud and nothing but fraud! After more then half a century of claiming that serotonin cures depression, now mainstream medicine is quietly trying to retreat from this fiasco by introducing more and more potent (and selective) serotonin antagonists as treatment of depression and silently phasing the SSRI drugs out. The study below is one of the most direct and damning pieces of evidence against the "serotonin deficiency hypothesis" as a cause of depression. A highly selective serotonin antagonist (primavanserin) was found to have potent anti-depressant effects in a human trial.
Pimavanserin - Wikipedia

This drug has no other effects except blocking the 5-HT2A (and to a smaller degree 5-HT2C) receptor. So, if this drug is a potent antidepressant then serotonin is a cause of depression, pure and simple. In addition, the drug's pharmacological profile also reveals another fraud - i.e. that schizophrenia is caused by too much dopamine. The drug is also used to treat schizophrenia, but unlike other drugs for the condition primavanserin has NO antagonism on dopamine receptors. In other words, it treats schizophrenia by blocking ONLY serotonin. I posted about this fraud in regard to schizophrenia several years ago when I pointed out that the main drug for treating schizoprenia (haloperidol) is actually a serotonin antagonist in addition to being dopamine antagonist.
Haloperidol - Wikipedia
For years, this information was concealed and only last month I noticed that the Wikipedia page for haloperidol has been updated to state that the drug is a serotonin antagonist as well. So, in case it is not clear yet let me say it loud and clear - serotonin causes BOTH depression and schizophrenia, and blocking serotonin may treat both conditions.

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Major Depressive Disorder - ICH GCP - Clinical Trials Registry
Add-on pimavanserin appears safe, effective in patients with major depression

"...Compared with placebo, pimavanserin reduced weighted HAMD-17 total scores in both stages (least-square means difference = –1.7; P = .04). Patients who received pimavanserin in the first stage separated from the placebo group on the HAMD-17 by the end of the first week (difference = –1.7; P = .04) and had significantly improved on the HAMD-17 by week 5 (difference = –4; P < .001)."

“This study indicates that pimavanserin, a molecule with a relatively unique pharmacological activity as a selective inverse agonist of the serotonin 5-HT2A receptor, may show antidepressant activity and could be a novel adjunctive treatment for patients who do not adequately respond to standard antidepressant therapy with either an SSRI or SNRI,” Maurizio Fava, MD, director of the division of clinical research of Massachusetts General Hospital Research Institute and executive vice chair of the hospital’s department of psychiatry, told Healio."

 

[Dobbler]

amazin
haidut for president

 

[Jeff Masters]

Great stuff Haidut, Apart from cyproheptadine what other products/foods/supplements may help to reduce serotonin?

 

[Lokzo]

Hip Hip Hooray... Nice finding yet again. Now, who's going to be the first on this forum to report back their experience...Or it's probably impossible to access.

 

[Lokzo]

Great stuff Haidut, Apart from cyproheptadine what other products/foods/supplements may help to reduce serotonin?

Shilajit is an obvious anti serotonin herb. However, you have to be VERY careful, since most Shilajit products are loaded with heavy metals!

 

[Soren]

On the daily mail uk today there are multiple stories warning about the dangers of anti-depressants I guess the pharmaceutical industry finally feels they have positioned themselves with new alternatives and they now are slowly letting slip the truth into the market. They are only 30 or 40 years late and god knows how many lives ruined.

Anti-depressants CAN ruin lives: Major U-turn as psychiatrists say millions of patients MUST be warned over severe side effects


DR MAX PEMBERTON: Never again must victims of the over-prescribing of anti-depressants be silenced or ignored

 

[ilhanxx]

I used cabergolin (dopamin agonist) , anything changed sexual or depression, only give me strong erection.

 

[Experienced]

Shilajit is an obvious anti serotonin herb. However, you have to be VERY careful, since most Shilajit products are loaded with heavy metals!

which one did you use? I`m planning on this one. Oriveda Medicinal Mushrooms is the COA Legit? if so I`m probably going to try to boost my T levels and down serotonin.

 

[daIllu]

These studies used SSRIs along with this serotonin antagonist, which is a strange combo if the SSRIs are supposed to raise the levels of serotonin.

 

[Source Code]

I asked chat gpt some questions about the migraine drug maxalt which is advertised as a serotonin agonist: me:Give detailed information regarding the exact mechanism of action of rizatriptan and it's supposed agonism or antagonism on 5ht receptors
Chatgpt:
Rizatriptan is a medication primarily used to treat migraine headaches. It belongs to a class of drugs known as triptans, which work by targeting specific serotonin (5-HT) receptors in the brain. Here's a detailed explanation of its mechanism of action:

1. **Serotonin Receptors (5-HT receptors):** Serotonin, also known as 5-hydroxytryptamine (5-HT), is a neurotransmitter that plays a crucial role in regulating various physiological processes, including mood, appetite, and pain perception. There are several types of serotonin receptors, but the ones most relevant to rizatriptan's mechanism of action are the 5-HT1B and 5-HT1D receptors.

2. **Agonism on 5-HT1B/1D receptors:** Rizatriptan is classified as a selective agonist for the 5-HT1B and 5-HT1D receptors. An agonist is a substance that binds to a receptor and activates it, producing a biological response. In this case, rizatriptan specifically targets the 5-HT1B and 5-HT1D receptors.

3. **Vasoconstriction:** When rizatriptan binds to the 5-HT1B/1D receptors located on the smooth muscle cells of certain blood vessels (particularly those in the brain), it triggers a cascade of events. One of the primary effects is vasoconstriction, which means the blood vessels constrict or narrow. This helps to reduce the dilation of blood vessels that occurs during a migraine attack, thereby relieving the associated pain.

4. **Inhibition of Neurogenic Inflammation:** Rizatriptan also inhibits the release of certain neuropeptides (substances involved in pain transmission) from nerve endings. This action helps to dampen the inflammation and pain signals associated with migraines.

5. **Central Nervous System Effects:** Rizatriptan also exerts effects on the central nervous system, but the exact mechanisms are not fully understood. It is believed to modulate the transmission of pain signals and reduce sensitization of neurons involved in pain perception.

6. **Absorption and Metabolism:** After oral administration, rizatriptan is rapidly absorbed from the gastrointestinal tract. It reaches peak plasma concentrations within about 1-1.5 hours. The liver metabolizes rizatriptan, primarily through the enzyme monoamine oxidase A (MAO-A) and other metabolic pathways.

7. **Excretion:** The metabolites of rizatriptan are excreted primarily in the urine.

Remember, this is a detailed explanation of the pharmacological action of rizatriptan. It's important to consult a healthcare professional for any specific medical advice or concerns.

Me:Are there any other antagonistic effects on other 5ht receptors

Chatgpt:
Rizatriptan primarily acts as an agonist on the 5-HT1B and 5-HT1D receptors. It has a higher affinity for these receptors compared to other serotonin receptors. However, rizatriptan may have some affinity for other subtypes of serotonin receptors, but this affinity is significantly lower and not considered clinically significant.

It's important to note that the selectivity of rizatriptan for 5-HT1B and 5-HT1D receptors is what makes it effective for treating migraines. By targeting these receptors, rizatriptan specifically addresses the vasodilation and inflammation associated with migraine attacks.

If you have concerns about specific interactions or effects, it's always best to consult with a healthcare professional or pharmacist who can provide the most up-to-date and relevant information based on your individual health circumstances.
Me:Be more specific for the affinity it has for the other receptors

Chatgpt:
Rizatriptan primarily exhibits high affinity for the 5-HT1B and 5-HT1D receptors, which are the main targets for its therapeutic effects in migraine treatment.

Regarding its affinity for other serotonin receptors, rizatriptan does have some level of binding affinity for certain other subtypes, but these interactions are notably weaker compared to its affinity for 5-HT1B and 5-HT1D. Specifically, rizatriptan may have lower affinity for 5-HT1F, 5-HT1A, 5-HT1E, and 5-HT7 receptors. However, it's important to emphasize that these interactions are not the primary mechanisms of action for rizatriptan, and their clinical significance in the context of migraine treatment is limited.

Keep in mind that the specifics of drug interactions and receptor affinities may be subject to ongoing research and updates beyond my last training data in September 2021. For the most current and detailed information, consulting medical literature or a healthcare professional with access to the latest research is advisable.

Me:Elaborate on the effects on 5-HT1F, 5-HT1A, 5-HT1E, and 5-HT7 receptors.

Chatgpt:
Rizatriptan primarily targets the 5-HT1B and 5-HT1D receptors, but it does have some affinity for other serotonin receptor subtypes, albeit to a lesser extent. Here's a brief overview of the potential effects on these receptors:

1. **5-HT1F Receptors:** Rizatriptan may have a modest affinity for 5-HT1F receptors. These receptors are found in the brain and are believed to play a role in migraine pathophysiology. Activation of 5-HT1F receptors can lead to vasoconstriction and inhibition of pain transmission, similar to the effects seen with 5-HT1B and 5-HT1D receptor activation. However, it's important to note that the affinity of rizatriptan for 5-HT1F receptors is lower compared to its primary targets.

2. **5-HT1A Receptors:** Rizatriptan may exhibit a weak affinity for 5-HT1A receptors. These receptors are widely distributed throughout the central nervous system and are involved in various functions, including mood regulation and anxiety. Activation of 5-HT1A receptors typically leads to inhibitory effects, which can include reduced neurotransmitter release. However, rizatriptan's affinity for 5-HT1A receptors is generally considered to be lower compared to its affinity for 5-HT1B and 5-HT1D receptors.

3. **5-HT1E Receptors:** Rizatriptan may also have a weak affinity for 5-HT1E receptors. These receptors are primarily located in the brain and are thought to be involved in the regulation of serotonin release. Activation of 5-HT1E receptors can lead to inhibition of serotonin release, which may modulate neurotransmission. Again, it's important to emphasize that rizatriptan's affinity for 5-HT1E receptors is relatively low compared to its primary targets.

4. **5-HT7 Receptors:** Rizatriptan may exhibit some weak affinity for 5-HT7 receptors. These receptors are widely distributed in the central nervous system and are implicated in mood regulation, sleep, and other functions. Activation of 5-HT7 receptors can lead to various effects, including modulation of neurotransmitter release.

It's important to note that while rizatriptan may have some affinity for these additional serotonin receptor subtypes, its primary therapeutic effects in migraine treatment are attributed to its actions on the 5-HT1B and 5-HT1D receptors. The affinity for these other receptors is generally weaker and may not significantly contribute to its clinical efficacy in treating migraines. Additionally, the specific details of these interactions may vary based on individual factors and may be subject to ongoing research.

Me:Elaborate on how much less the affinity is for these other receptors

Chatgpt:
I don't have access to specific numerical values for the binding affinities of rizatriptan to various serotonin receptors beyond my last training data in September 2021. The relative affinity of a drug for different receptor subtypes can be a complex and dynamic area of pharmacology research, and it's important to note that these values may be proprietary information held by pharmaceutical companies.

If you require precise numerical data on the binding affinities of rizatriptan for specific serotonin receptor subtypes, I recommend consulting scientific literature, clinical studies, or authoritative pharmacology sources. Additionally, a healthcare professional or pharmacist with access to specialized databases and resources may be able to provide more detailed information.


It took a while but it seems that if you dig deep enough many of these ssri's that users report any positive effect from seem to actually lower serotonin and no numerical value of how much lower the affinity to those receptors is given so maybe they just attribute the benefits to agonist effect?

 

[dukesbobby777]

I asked chat gpt some questions about the migraine drug maxalt which is advertised as a serotonin agonist: me:Give detailed information regarding the exact mechanism of action of rizatriptan and it's supposed agonism or antagonism on 5ht receptors
Chatgpt:
Rizatriptan is a medication primarily used to treat migraine headaches. It belongs to a class of drugs known as triptans, which work by targeting specific serotonin (5-HT) receptors in the brain. Here's a detailed explanation of its mechanism of action:

1. **Serotonin Receptors (5-HT receptors):** Serotonin, also known as 5-hydroxytryptamine (5-HT), is a neurotransmitter that plays a crucial role in regulating various physiological processes, including mood, appetite, and pain perception. There are several types of serotonin receptors, but the ones most relevant to rizatriptan's mechanism of action are the 5-HT1B and 5-HT1D receptors.

2. **Agonism on 5-HT1B/1D receptors:** Rizatriptan is classified as a selective agonist for the 5-HT1B and 5-HT1D receptors. An agonist is a substance that binds to a receptor and activates it, producing a biological response. In this case, rizatriptan specifically targets the 5-HT1B and 5-HT1D receptors.

3. **Vasoconstriction:** When rizatriptan binds to the 5-HT1B/1D receptors located on the smooth muscle cells of certain blood vessels (particularly those in the brain), it triggers a cascade of events. One of the primary effects is vasoconstriction, which means the blood vessels constrict or narrow. This helps to reduce the dilation of blood vessels that occurs during a migraine attack, thereby relieving the associated pain.

4. **Inhibition of Neurogenic Inflammation:** Rizatriptan also inhibits the release of certain neuropeptides (substances involved in pain transmission) from nerve endings. This action helps to dampen the inflammation and pain signals associated with migraines.

5. **Central Nervous System Effects:** Rizatriptan also exerts effects on the central nervous system, but the exact mechanisms are not fully understood. It is believed to modulate the transmission of pain signals and reduce sensitization of neurons involved in pain perception.

6. **Absorption and Metabolism:** After oral administration, rizatriptan is rapidly absorbed from the gastrointestinal tract. It reaches peak plasma concentrations within about 1-1.5 hours. The liver metabolizes rizatriptan, primarily through the enzyme monoamine oxidase A (MAO-A) and other metabolic pathways.

7. **Excretion:** The metabolites of rizatriptan are excreted primarily in the urine.

Remember, this is a detailed explanation of the pharmacological action of rizatriptan. It's important to consult a healthcare professional for any specific medical advice or concerns.

Me:Are there any other antagonistic effects on other 5ht receptors

Chatgpt:
Rizatriptan primarily acts as an agonist on the 5-HT1B and 5-HT1D receptors. It has a higher affinity for these receptors compared to other serotonin receptors. However, rizatriptan may have some affinity for other subtypes of serotonin receptors, but this affinity is significantly lower and not considered clinically significant.

It's important to note that the selectivity of rizatriptan for 5-HT1B and 5-HT1D receptors is what makes it effective for treating migraines. By targeting these receptors, rizatriptan specifically addresses the vasodilation and inflammation associated with migraine attacks.

If you have concerns about specific interactions or effects, it's always best to consult with a healthcare professional or pharmacist who can provide the most up-to-date and relevant information based on your individual health circumstances.
Me:Be more specific for the affinity it has for the other receptors

Chatgpt:
Rizatriptan primarily exhibits high affinity for the 5-HT1B and 5-HT1D receptors, which are the main targets for its therapeutic effects in migraine treatment.

Regarding its affinity for other serotonin receptors, rizatriptan does have some level of binding affinity for certain other subtypes, but these interactions are notably weaker compared to its affinity for 5-HT1B and 5-HT1D. Specifically, rizatriptan may have lower affinity for 5-HT1F, 5-HT1A, 5-HT1E, and 5-HT7 receptors. However, it's important to emphasize that these interactions are not the primary mechanisms of action for rizatriptan, and their clinical significance in the context of migraine treatment is limited.

Keep in mind that the specifics of drug interactions and receptor affinities may be subject to ongoing research and updates beyond my last training data in September 2021. For the most current and detailed information, consulting medical literature or a healthcare professional with access to the latest research is advisable.

Me:Elaborate on the effects on 5-HT1F, 5-HT1A, 5-HT1E, and 5-HT7 receptors.

Chatgpt:
Rizatriptan primarily targets the 5-HT1B and 5-HT1D receptors, but it does have some affinity for other serotonin receptor subtypes, albeit to a lesser extent. Here's a brief overview of the potential effects on these receptors:

1. **5-HT1F Receptors:** Rizatriptan may have a modest affinity for 5-HT1F receptors. These receptors are found in the brain and are believed to play a role in migraine pathophysiology. Activation of 5-HT1F receptors can lead to vasoconstriction and inhibition of pain transmission, similar to the effects seen with 5-HT1B and 5-HT1D receptor activation. However, it's important to note that the affinity of rizatriptan for 5-HT1F receptors is lower compared to its primary targets.

2. **5-HT1A Receptors:** Rizatriptan may exhibit a weak affinity for 5-HT1A receptors. These receptors are widely distributed throughout the central nervous system and are involved in various functions, including mood regulation and anxiety. Activation of 5-HT1A receptors typically leads to inhibitory effects, which can include reduced neurotransmitter release. However, rizatriptan's affinity for 5-HT1A receptors is generally considered to be lower compared to its affinity for 5-HT1B and 5-HT1D receptors.

3. **5-HT1E Receptors:** Rizatriptan may also have a weak affinity for 5-HT1E receptors. These receptors are primarily located in the brain and are thought to be involved in the regulation of serotonin release. Activation of 5-HT1E receptors can lead to inhibition of serotonin release, which may modulate neurotransmission. Again, it's important to emphasize that rizatriptan's affinity for 5-HT1E receptors is relatively low compared to its primary targets.

4. **5-HT7 Receptors:** Rizatriptan may exhibit some weak affinity for 5-HT7 receptors. These receptors are widely distributed in the central nervous system and are implicated in mood regulation, sleep, and other functions. Activation of 5-HT7 receptors can lead to various effects, including modulation of neurotransmitter release.

It's important to note that while rizatriptan may have some affinity for these additional serotonin receptor subtypes, its primary therapeutic effects in migraine treatment are attributed to its actions on the 5-HT1B and 5-HT1D receptors. The affinity for these other receptors is generally weaker and may not significantly contribute to its clinical efficacy in treating migraines. Additionally, the specific details of these interactions may vary based on individual factors and may be subject to ongoing research.

Me:Elaborate on how much less the affinity is for these other receptors

Chatgpt:
I don't have access to specific numerical values for the binding affinities of rizatriptan to various serotonin receptors beyond my last training data in September 2021. The relative affinity of a drug for different receptor subtypes can be a complex and dynamic area of pharmacology research, and it's important to note that these values may be proprietary information held by pharmaceutical companies.

If you require precise numerical data on the binding affinities of rizatriptan for specific serotonin receptor subtypes, I recommend consulting scientific literature, clinical studies, or authoritative pharmacology sources. Additionally, a healthcare professional or pharmacist with access to specialized databases and resources may be able to provide more detailed information.


It took a while but it seems that if you dig deep enough many of these ssri's that users report any positive effect from seem to actually lower serotonin and no numerical value of how much lower the affinity to those receptors is given so maybe they just attribute the benefits to agonist effect?

What am I learning here? Couldn't you have asked it about a more useful pharmaceutical?

 

[Source Code]

Sorry if it's not useful, a relative of mine takes it for migraines because it's the only thing that works for them.i told them they should just try cyproheptadine. What I learnt is although everywhere you search online the only thing you find about this particular SSRI is that it's a serotonin agonist. But through a deeper search I finally found it is actually an antagonist. And also the chatgpt ai search seemed very reluctant to reveal this information.
I can search about other things if you'd like.I just thought it seemed relevant to some of Haiduts writings about serotonin and SSRI's.

I found it quite shocking.

Sorry again if it was too long-winded I didn't mean to derail the thread