Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia


Wasn’t able to read the full paper but …

In this paper, we discuss how a better understanding of these challenges has shaped our proposed experimental design for testing a new D1R/D5R partial agonist, PF-06412562, renamed CVL-562

I found this clinical trial underway:

This study will test whether CVL-562 (PF-06412562), a dopamine 1 partial agonist novel compound, affects working memory neural circuits in patients with early episode schizophrenia. The overall aim is to establish neuroimaging biomarkers of the Dopamine Receptor 1/Dopamine Receptor 5 Family (D1R/D5R) target engagement to accelerate development of D1R/D5R agonists in humans to treat cognitive impairments that underlie functional disability in schizophrenia, a key unaddressed clinical and public health concern.

For whatever reason, this drug does not seem to be listed on Cerevel’s web page.


Despite all diagnostic symptoms
There is nothing (anything) in the Sz condition that arise from an inherited autogenous defects or acquired defects through the experience of psychological coexistence

2-There is no organic change that precedes the occurrence of sz
3-The sz condition itself does not arise from appearance of an abnormal chemical substance in the anatomical structure AT ALL
4-The effect of sz (who is represented in the psychotic factor) is not followed by appearance of an abnormal chemical substance OR a permanent change in the anatomical structure
5- the effect of sz does not causing a permanent disease located in the biological structure
6-The core effect of sz condition on the human basic nature causes an acquired defect in the cognitive aspect without inducing a pathological change in the cellular structures or in brain substances
7-The effect causing an acquisition of cognitive defects after occurrence of mental processing to the output data
8- the alteration occurs after the ending of the mental processing to self-idea data
9-The main alteration occurs ONLY in the concept of the cognitive material transmitted by neurotransmitters AND does not aiming to change the raw substance of the neurotransmitter itself !
10- in the case,if a change occurs in the neurotransmitter material (for any reason) this will led to the absence of an intentional alteration in the concept of the transferred knowledge material !

In summary,there is NO any biological permanent change or self-cognitive impairments causing the sz or its symptoms !

How do neurotransmitters work during deep sleep, loss of consciousness and dreaming events ?
What is the rate of secretion or lack of secretion of those transmitters during those periods ?

If you know the actual answers,you will touch by your finger the optimum level of mental chemistry at which the sz condition itself and all its bad side symptoms disappear completely !!

After the onset of sz condition during the first month,the drugs that cause the state of deep sleep,loss of self-consciousness are considered the optimum intervention (treatment in the go) that erase the sz condition existentially and blocking its functional symptoms one and for all !

But after waking up from sleep and beginning the activity of self-transmitters ,the situation Changes !

With the lowest amount excreted from these transmitters(in the waking case) to the extent that it is not enough for transfer any self-data between regions of brain cells ,and be enough for a sense of self or transfers the person’s state from a state of not feeling self to a state of feeling it,
It is considered the starting spark that help to the emergence of the sz condition internally represented by the psychotic emitter ,who is starts his independent /interfering functions which induces all kinds of symptoms at the mental events,emotional,movement,behaviors and the balance’s cuff of forward /reverse chemical processes that accompany any mental processes

In the waking time,even if you don"t thinking in a thing (anything) you will listen inwardly to the vocal inspiration of the psychotic emitter (it is vocal thoughts)

while you perceive that,your self-thoughts is not vocal at all
they are secreted internally by non-acoustically speaking mechanism,do not listen to them as vocalized voices,instead,you realize what it means

Bypassing the delusional diagnosis of a disease material embodied in the organic structures
In the case,if you do not know clearly what is the essential nature of the sz as a Whole condition

what is the logic be used for searching about casual factors that cause the sz,increase the risks of developing it or/ even contribute to its creation ?

In the case,if you think that the sz is a disease (any disease)
The disease is a kind of change (alteration /modification) in something
So,what is the core principle of the change (if it was existed) ?

what is the cause of existence (Reason d’etre ) ?
What is the functional cause ?
What is the active material ?
What is the effect’s mechanism ?
(reactions and reactions )
What is the place/speed and rates of interactions /reactions in time unites ?

How all of these translated into the language of the extreme thinking,feelings and behaviors in most of daily life events to hurt oneself or others ?