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5-HT2a antagonists as anti-psychotics?

SpunkySkunk347

SpunkySkunk347

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It really doesn't make sense to me how drugs such as Quetiapine achieve their supposed "anti-psychotic" effects.

My first impression would be that antagonism of 5-HT2a receptors would worsen the negative symptoms of a psychosis by causing confusion and cognitive dissonance.

Also, wouldn't the anticholinergic effects of such drugs contribute to psychosis? Short-term memory impairment is perhaps the main underlying attribute of a psychosis -- wouldn't anticholinergic activity worsen problems with short-term memory?

It seems that such antipsychotics could only be considered effective for combating the positive symptoms of psychosis -- and this is done merely as the result of sedation.

Wouldn't other drugs be much more viable alternatives for treating psychotic symptoms? Such as:
- "Top-down" benzodiazepines such as diazepam, which would: A) Alleviate a psychotic individual's frustration with cognitive dissonance ("disorganized" psychoses in particular), thereby nipping the "downward spiral" effect of psychosis in the bud; B) Sedate the individual, combating the positive symptoms of psychosis.

- Opiates, which would halt the cyclical thinking associated with obsessive-compulsive anxiety. Also, would sedate the individual and remedy any panic/terror the psychotic individual is experiencing.

Instead, we have an assortment of "anti-psychotic" drugs that induce delirium and akathisia.
 
Probably because they're less addicting and don't have any recreational value at all... those bastards.
 
Completely agree with you.

An anti-psychotic should only block dopamine

Quetiapine blocks 5-ht and many other things, such as histamine lol - wtf?

Quetiapine is flawed science in my opinion, the only way it would help with psychosis is the dopamine blocking action, but it blocks lots of other things too like seretonin (causing depression, confusion, loss of motivation, etc)

They should use a drug that ONLY blocks dopamine as anti-psychotic.



Quetiapine is ideal for me personally if I took too much MDMA and it blocks it. (*not medical advice*)
 
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Tromps said:
Probably because they're less addicting and don't have any recreational value at all... those bastards.
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Yep.
I've read quite a bit of material that suggests that opiates can not only alleviate OCD-esque symptoms, but a single opiate session can seemingly cure OCD for weeks/months.

Our society's mental health system has its thumb up its ass.
 
Brian.Badonde said:
An anti-psychotic should only block dopamine
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That was the original plan. But the extrapyramidal side effects and tardive diskinesia seen in the 1st generation antipsychotics steered the market away from it. Rightfully so perhaps: EPS sucks, and TD is something you'd hesitate to wish on your worse enemy.

There are novel mechanisms in progress, such as glycine transporter antagonism.
 
The full antagonists are certainly bad, but some of the low low efficacy partial agonists have been effectively, IIRC.

glycine receptors seem to be the potential target for all sorts of stuff now. They're certainly promising.
 
Trust me, if these other drugs like benzodiazepines showed clinical efficacy in treating schizophrenia, drug companies would already be fighting over eachother to get their drugs prescribed to any and every person with schizophrenia. Benzos actually sometimes make psychotics more violent because of their ability to reduce inhibitions and impulse control.
 
Cannabidiol shows promise in treating schizophrenia.

http://dx.doi.org/10.1016/S0924-9338(09)70440-7

I have a hunch that other 5-ht1a agonists, like pFPP, will also show some efficacy in schizophrenia. The reasoning is that the resultant oxytocin release will alleviate antisocial behaviors associated with schizophrenia. Analgesia never hurt either.

The resultant inhibition of learning and memory is concerning. Maybe in combination with some sort of nootropic.
 
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atara said:
Analgesia never hurt either.
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lol/qft

Also I agree that CBD and possibly some other minor cannabis alkaloids do show promise for new antipsychotic treatments.

Are there any effective antipsychotics that don't sedate patients past the point of being able to cause any trouble?
 
“I” had my fair go with Quetiapine. It can help with getting in touch with the ground. It's worked for mixed states well for me. Makes me feel the way I did before I got into drugs.

The anticholinergic effect if anything might increase negative symptoms more so than the serotonergic effects. 5-HT antagonism (basically opposite of LSD?) making the voices harder to hear. So it removes positive symptoms that way.

A high degree of self-control is needed with benzos. I don't think most docs trust quasi-psychotics with benzos...

Well technically speaking nicotine also has some potential against OCD...
 
nuke said:
Trust me, if these other drugs like benzodiazepines showed clinical efficacy in treating schizophrenia, drug companies would already be fighting over eachother to get their drugs prescribed to any and every person with schizophrenia. Benzos actually sometimes make psychotics more violent because of their ability to reduce inhibitions and impulse control.
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depends on the type of psychosis we're talking about here.
Benzodiazepines can, and sometimes are, used to treat catatonic psychosis.

And as for other types of psychosis being treated with benzos, here was an inconclusive study done on the subject:
http://www2.cochrane.org/reviews/en/ab006391.html

Most stimulant/meth/amphetamine users on this forum will give you their word that benzodiazepines are the ideal drug for dealing with a stimulant psychosis.
 
any major dude said:
lol/qft

Also I agree that CBD and possibly some other minor cannabis alkaloids do show promise for new antipsychotic treatments.

Are there any effective antipsychotics that don't sedate patients past the point of being able to cause any trouble?
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Aripiprazole. Its 5ht2c agonism makes it cause some restlessness, but it is also the first antipsychotic not to cause weight gain. "Side effects" lists both insomnia and sleepiness, which is either hilarious or sad.

Amisulpiride, sulpiride, and sultopride as well, as they activate the GHB receptor, which has stimulant effects. However, they're not available in the US. The GHB receptor may turn out to be an effective target for antipsychotics.
 
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1. Geodon (ziprasidone) doesn't cause weight gain and yields only mild sedation.

2. I'd take one of the newer generation 5ht2a/D2 antagonists such as Zyprexa (olanzapine) or Seroquel (quetiapine) over one of the older D2 antagonists such as stelazine or thorazine or haldol any day. Extrapyramidal side effects of the older drugs are excruciatingly uncomfortable!

3. Benzodiazepines can be helpful in amphetamine psychosis but they don't compare to the atypicals--the atypicals are much better for coming down from a long tweak session.

4. The newer atypicals are abominably overpriced. A bottle of thirty 20mg Zyprexa's goes for just under $900 for a 30 day supply.
 
any major dude said:
Are there any effective antipsychotics that don't sedate patients past the point of being able to cause any trouble?
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Ondansetron, an antagonist which is selective for 5-HT3.

(incidentally, granisetron has more than 3 times the potency of ondansetron)
 
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