Towards Novel Treatments for Schizophrenia: Molecular and Behavioural Signatures of the Psychotropic Agent SEP-363856

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In this study, we investigated the ability of an acute oral SEP-856 administration to modulate the functional activity of specific brain regions at basal levels and under glutamatergic or dopaminergic-perturbed conditions in adult rats. We found that immediate-early genes (IEGs) expression was strongly upregulated in the prefrontal cortex and, to a less extent, in the ventral hippocampus, suggesting an activation of these regions.

Sounds like a really different medication.

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What is the significance of the bolded part below?

Furthermore, SEP-856 was effective in preventing the hyperactivity induced by an acute injection of phencyclidine (PCP), but not of d-amphetamine (AMPH)

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They use those two drugs to test the probable antipsychotic efficacy in animals. It worked with one but not the other. This might suggest a different mechanism of action (because it works with one and not the other) but that’s over my pay grade.

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I’m sick of animal studies because a rat can’t tell you how they feel. It probably helped the rats but the rat probably feels like ■■■■ inside.

I wonder what messed up side effects this drug has.

Here is one interesting video about SEP-363856 New Drug For Schizophrenia #newsunoviondrug - YouTube

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Well, this one is already in human testing. With fairly good results so far but I believe just in phase 2 now.

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In phase 3: Sunovion | Sunovion – Pipeline and probably on market for 2 years.

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@Minion

That video was very informative, thanks.

Shame that caplyta was such a fail.

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@twinklestars @Minion

How is decreasing dopamine different from blocking it?
In both cases there is reduction of dopamine function so should be similar side effects.

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I think the ideal would be to have your brain just make the correct amount in the correct place and at the correct time. Blocking it in areas that it doesn’t need to be blocked, (along with areas that it does) is going to cause some side effects. So if this manages to modulate the production of dopamine so that it is closer to normal, that would be better than blocking it after the fact.

Excess dopamine release might also be pretty far down the cascade of issues leading to symptoms, so if this acts earlier in that cycle, that also might be good.

The gene expression effects of this drug though are really interesting.

Acute SEP-856 Administration Up-Regulates the Expression of Activity-Regulated Genes with Anatomical Selectivity

As a first step, we investigated the ability of SEP-856 to modulate the activity of different brain regions after acute administration. First we measured the expression of the activity-regulated cytoskeleton associated protein (Arc), an immediate-early gene involved in neuroplasticity, determining memory formation and sustaining cognitive processes Arc mRNA levels were significantly modulated by SEP-856 treatment in the PFC and ventral-HIP. In detail, SEP-856 treatment strongly upregulated the expression of Arc in the PFC at all doses tested.

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Thanks, hopefully it will be good for negative symptoms.

@twinklestars

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I’m not an expert, but I think it’s something about TAAR1 receptor and reducing dopamine but not blocking it…(like it’s said on the video a posted before) that could be solution for the negative symptoms.

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I mean if you are that much skeptical of new medicine, you can always stick to older medicine. Caplyta imo is better than a lot of old medicine just that it makes you more sedated than most of the older medicine but with less of other side effects

@swordiebrom

Have you ever tried Abilify?

Yes on it for a year, it sucks I still have weight gain and it made me to be more easily sexual aroused, also have muscle spasms here and there and akathisa at high dose of 25 mg. Also, at 10mg it made my mouth so dry to the extent that I have sensitive teeth and couldn’t eat anything too hot or cold so I had to switch to latuda. Caplyta makes me more sedated, with sensitive teeth and nothing else, was also able to lose a few kg on it while Latuda is about the same as abilify without the sexual side effects

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