Disappointing outcome of bitopertin treatment for negative symptoms

Medications
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Another one bites the dust. At phase 3.

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Wild swings in the dark. That’s what current attempts are, because the etiology of NS is still a mystery…

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Actually - this is a report on a drug that was cancelled about 2 years ago I think.

But - if you’re interested - here is the full research paper for the above study summary:

http://sci-hub.cc/10.1016/j.biopsych.2016.11.014

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Stoopid sciencedaily.com . :blush:

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Wouldn’t it be a hoot if all psych meds in the future were only an Rx of exercise daily?

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Apparently exercise is great for schizophrenia. If you can get motivated to do it that is.

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Still don’t know why they’re goin the serotonergic route with min-101, seems like it couldn’t be further off the target.

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Because binding of a different ligand may trigger a different response in the same receptor(s). LSD binds to serotonin receptors and affects them in a totally different way than regular serotonin does.

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I think Lsd agonizes serotonin 2a receptor subtype, which causes mostly visual hallucinations, right? Lsd binds tightly enough to cause an abnormally high release of serotonin in these receptors.

I don’t know what that has to do with min-101 other than that it inhibits the same receptors. In theory that should increase dopamine release in the prefrontal cortex improving negative symptoms.

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Didn’t bitopertin already fail back in like 2012? Good to see they are still testing it, it was supposed to be our saviour from negative sx. It certainly got its share of talking up.

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Are you familiar with ‘functional selectivity’ or ‘biased agonism’? According to classical conxepts of receptor pharmcology one would predict that any drug that activates 5ht2a serotonin receptors will be hallucinogenic but functional selectivity describe the phenomenon whereby different drugs acting at the same receptor subtype can produce diverse phisiological effects. Min-101 is no exception. In other words “an agonist is an agonist is an agonist” is not entirely true. Thus, for example the LSD analogue lisuride, which is prescribed in Europe for Parkinson’s disease, is a potent 5ht2a agonist devoid of appreciable hallucinogenic actions. This is a challenge for pharmaceutical research.

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Thanks for explaining that to me. Perhaps this explains why everything which inhibits 5th2a isn’t cut out to be an antipsychotic. They don’t produce he same physiological effect. If that were the case Trazodone would could be used as an antipsychotic for 3 dollars a week.

Now the question is, how to the drug developers know whether or not min-101 will work for psychosis or negative symptoms? Does it have something to do with the affinity with which the drug binds to a receptor. The action at that receptor? Please inform me.

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Interesting that they want to improve negative sx by increasing dopamine in the prefrontal cortex. We have just read in this article that excessive excitation is possibly detrimental for cognition.

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I think that (article) was about GABA-ergic drugs. Although I’m sure it’s more than just that.

Maybe it was a different article. Going by memory, which is iffy. Hehe.

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Sorry, I just assumed that excitation in general is bad for cognition.

I’m going by memory too, and possibly cursory reading.

I think dopamine is an excitatory neurotransmitter and GABA is inhibitiory.

So too much dopamine in that region might mean worse cognition, not better.

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Are you saying pharmaceutical research is simply trial and error at this point? In other words in the drug pamphlets when they say that “the reason this drug works for psychosis is unknown” they are telling the truth.

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Typically, it’s through animal testing and much extrapolation. Drug developers have to examine multiple signaling pathways to link pathway activities to physiologic functions and pharmacological activity. Detection is achieved by comparing ligand activity at a given signaling pathway to that of a reference compound. For example, catechol seems to be an effective molecular probe to differentiate mechanistic differences between β-adrenergic receptor activation by catecholamine agonists. But the effects of a therapeutic in humans cannot be fully predicted until rigorous clinical testing occurs with adequete follow up.

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Short answer: yes. I recommend you take a look at the introductory paragraph of this article https://www.fda.gov/aboutfda/whatwedo/history/overviews/ucm304485.htm

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