Novel GPR139 agonist evaluated in schizophrenia mouse model


Sure, I can summarize the article for you. Here is a brief summary:

The article reports on a novel GPR139 agonist, named TAK-041, that was evaluated in a mouse model of schizophrenia. GPR139 is a receptor that is mainly expressed in the brain, especially in the habenula, a region involved in reward and motivation. The article explains that the habenula is implicated in schizophrenia, as it shows abnormal activity in response to negative outcomes. The article also cites previous studies that showed that TAK-041 can reverse anhedonia and social interaction deficits in rodent models of depression and schizophrenia. The article then describes the results of the new study, which showed that TAK-041 improved cognitive and social impairments in mice with a genetic mutation that mimics schizophrenia. The article suggests that TAK-041 may modulate the habenula circuitry and restore the balance between excitatory and inhibitory neurotransmission in the brain. The article concludes that TAK-041 is a promising candidate for the treatment of negative symptoms in schizophrenia.


Judging by a Google Scholar search, it was only tested in humans with schizophrenia in a safety study, reported in 2022.

Also for some reason I can’t read the original text. The website asks me for thousands of dollars in reply.

Curious, from a 2022 review:

Furthermore, mice lacking GPR139 exhibited complete loss of pre-pulse inhibition and developed spontaneous ‘hallucinogenic’ head-twitches, altogether suggesting schizophrenia-like symptomatology.

I’m not sure about the head twitches, but decreased PPI has indeed been long associated with schizophrenia.

Looks like the intended INN for TAK-041 is Zelatriazin.

Interesting. Work is already underway to develop further molecules based on TAK-041, as reported in a recent publication. They came up with three new variations of the molecule, which could act better / stronger upon the same receptor.

Let’s hope that this activity indicates that the receptor is really something useful for patients.