Inhibition of phosphodiesterase 2 by Bay 60-7550 decreases ethanol intake and preference in mice

Shi, Jing; Liu, Huaxia; Pan, Jianchun; Chen, Jie; Zhang, Nianping; Liu, Kaiping; Fei, Ning; O’Donnell, James M.; Zhang, Han‐Ting; Xu, Ying

doi:10.1007/s00213-018-4934-4

Cited by 2 publications

(1 citation statement)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported to have anxiolytic properties and to ameliorate learning, memory, and synaptic plasticity in normal animals [64][65][66] and in neurodegeneration models [67,68]. This drug could also be used for treatment of alcoholism since it was reported to decrease ethanol intake and preference in mice [69]. Despite all these results, no clinical trials testing Bay 60-7550 have been reported, suggesting possible toxicity of this compound.…”

Section: Pharmacological Modulation Of Pdesmentioning

confidence: 99%

Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders

Delhaye

Bardoni

2021

Mol Psychiatry

View full text Add to dashboard Cite

Phosphodiesterases (PDEs) are enzymes involved in the homeostasis of both cAMP and cGMP. They are members of a family of proteins that includes 11 subfamilies with different substrate specificities. Their main function is to catalyze the hydrolysis of cAMP, cGMP, or both. cAMP and cGMP are two key second messengers that modulate a wide array of intracellular processes and neurobehavioral functions, including memory and cognition. Even if these enzymes are present in all tissues, we focused on those PDEs that are expressed in the brain. We took into consideration genetic variants in patients affected by neurodevelopmental disorders, phenotypes of animal models, and pharmacological effects of PDE inhibitors, a class of drugs in rapid evolution and increasing application to brain disorders. Collectively, these data indicate the potential of PDE modulators to treat neurodevelopmental diseases characterized by learning and memory impairment, alteration of behaviors associated with depression, and deficits in social interaction. Indeed, clinical trials are in progress to treat patients with Alzheimer’s disease, schizophrenia, depression, and autism spectrum disorders. Among the most recent results, the application of some PDE inhibitors (PDE2A, PDE3, PDE4/4D, and PDE10A) to treat neurodevelopmental diseases, including autism spectrum disorders and intellectual disability, is a significant advance, since no specific therapies are available for these disorders that have a large prevalence. In addition, to highlight the role of several PDEs in normal and pathological neurodevelopment, we focused here on the deregulation of cAMP and/or cGMP in Down Syndrome, Fragile X Syndrome, Rett Syndrome, and intellectual disability associated with the CC2D1A gene.

show abstract

Section: Pharmacological Modulation Of Pdesmentioning

confidence: 99%

Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders

Delhaye

Bardoni

2021

Mol Psychiatry

View full text Add to dashboard Cite

show abstract

Cyclic Nucleotide Phosphodiesterases in Alcohol Use Disorders: Involving Gut Microbiota

Hou

Rong

Zhang

et al. 2022

International Journal of Neuropsychopharmacology

View full text Add to dashboard Cite

Alcohol abuse is one of the most significant public health problems. Chronic, excessive alcohol consumption not only causes alcohol use disorder (AUD), but also changes the gut/lung microbiota, including bacterial and non-bacterial types. Both types of microbiota can release toxins, further damage the gastrointestinal/respiratory tracts, cause inflammation, and impair the functions of the liver, lung and brain, which in turn deteriorates AUD. Phosphodiesterases (PDEs) are critical in the control of intracellular cyclic nucleotides, including cyclic AMP (cAMP) and cyclic GMP (cGMP). Inhibition of certain host PDEs reduces alcohol consumption and attenuates alcohol-related impairment. PDEs are also expressed in the microbiota and may play a potential role in controlling microbiota-associated inflammation. Here, we first summarize the influences of alcohol on gut/lung bacterial and non-bacterial microbiota, as well as on the gut-liver/brain/lung axis. We then discuss the relationship between gut/lung microbiota-mediated PDE signaling and AUD consequences, in addition to highlighting PDEs as potential targets for treatment of AUD.

show abstract

Inhibition of phosphodiesterase 2 by Bay 60-7550 decreases ethanol intake and preference in mice

Abstract: The results suggest that PDE2 plays a role in the regulation of ethanol consumption and that PDE2 inhibitors may be a novel class of drugs for treatment of alcoholism.

Cited by 2 publications

References 51 publications

Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders

Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders

Cyclic Nucleotide Phosphodiesterases in Alcohol Use Disorders: Involving Gut Microbiota

Contact Info

Product

Resources

About