Antipsychotic-like effects of a novel phosphodiesterase 10A inhibitor MT-3014 in rats

Takakuwa, Misae; Watanabe, Yumi; Saijo, Takeaki; Murata, Meguru; Anabuki, Jun; Tezuka, Tomoaki; Sato, Saori; Kojima, Kanako; Hashimoto, Kenji

doi:10.1016/j.pbb.2020.172972

Cited by 5 publications

(2 citation statements)

References 43 publications

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“…Papaverine is known to improve cAMP and pCREB levels via the cAMP/CREB pathway in both cerebellum and frontal cortex, areas of brain indicated to play a major role in locomotor activity (Rodefer et al., 2005; Weber et al., 2009). As reported impairments in behaviour such as hyperactivity may result from reduced pCREB and BDNF (Yuan et al., 2019) and it now understood that hyperactivity is reduced by PDE10A inhibition (Harada et al., 2020; Takakuwa et al., 2020). Similarly, in the present study animals in the papaverine treatment groups showed improvement in aforementioned markers compared to the PAE group.…”

Section: Discussionmentioning

confidence: 99%

Papaverine ameliorates prenatal alcohol‐induced experimental attention deficit hyperactivity disorder by regulating neuronal function, inflammation, and oxidative stress

Sharma

Dhiman

Golani

et al. 2020

Intl J of Devlp Neuroscience

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Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with complex aetiology and phenotypes. Phosphodiesterase10A (PDE10A) has been shown to provide benefits in various brain conditions. We investigated the role of papaverine, a selective PDE10A inhibitor on core phenotypes in prenatal alcohol exposure (PAE) model of ADHD. In order to identify probable mechanisms involved, the effects on several protein markers of neuronal function such as, neuronal survival‐BDNF, neuronal transcription factor‐pCREB, brain inflammation (IL‐6, IL‐10, and TNF‐α), and brain oxidative stress (TBARS and GSH) were studied in frontal cortex, cerebellum, and striatum. PAE resulting hyper‐locomotion, inattention, and anxiety were studied by the use of open‐field, y‐maze, and elevated plus maze, respectively. Administration of papaverine (15/30 mg kg−1) to PAE group of animals resulted in amelioration of hyperactivity, inattention, and anxiety. Also, papaverine resulted in significant increase of the levels in BDNF, pCREB, IL‐10, and GSH along with significant decrease of TNF‐α, IL‐6, and TBARS in different brain areas of PAE group. Papaverine, a selective PDE10A inhibitor rectified behavioural phenotypes associated with ADHD, possibly by altering the protein markers associated with neuronal survival, neuronal transcription factor, brain inflammation, and brain oxidative stress. Implicating PDE10A as a possible target for furthering our understanding of ADHD phenotypes.

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Section: Discussionmentioning

confidence: 99%

Papaverine ameliorates prenatal alcohol‐induced experimental attention deficit hyperactivity disorder by regulating neuronal function, inflammation, and oxidative stress

Sharma

Dhiman

Golani

et al. 2020

Intl J of Devlp Neuroscience

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“…Phosphodiesterase 10 (PDE10) has been described as a promising target for the treatment of many neurodegenerative and psychiatric diseases (see [ 216 ] for a review). Its blockage in animal models of schizophrenia using rodents and apes induces a beneficial effect in cognitive deficit [ 217 , 218 ]. TAK-063, a PDE10 inhibitor, has reached clinical trials, and although it was shown to be safe in phase 1 [ 219 ], it did not show a significant improvement in cognitive abilities in phase 2 studies with schizophrenic patients [ 119 ].…”

Section: Treatment Of Cognitive Deficit In Schizophreniamentioning

confidence: 99%

Cognitive Deficit in Schizophrenia: From Etiology to Novel Treatments

Martínez

Brea

Rico

et al. 2021

IJMS

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Schizophrenia is a major mental illness characterized by positive and negative symptoms, and by cognitive deficit. Although cognitive impairment is disabling for patients, it has been largely neglected in the treatment of schizophrenia. There are several reasons for this lack of treatments for cognitive deficit, but the complexity of its etiology—in which neuroanatomic, biochemical and genetic factors concur—has contributed to the lack of effective treatments. In the last few years, there have been several attempts to develop novel drugs for the treatment of cognitive impairment in schizophrenia. Despite these efforts, little progress has been made. The latest findings point to the importance of developing personalized treatments for schizophrenia which enhance neuroplasticity, and of combining pharmacological treatments with non-pharmacological measures.

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