Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The harmful effects caused by misuse of psychoactive substances have raised both medical and social problems. Substance dependence is a chronic relapsing disorder, which appears to involve neuroadaptive changes in cellular signaling and downstream gene expression. The unchanged consumption of present substances and increasing demand for new psychostimulants make the development of novel management/treatment strategies challenging. Emerging evidence has shown that the cyclic AMP (cAMP) signaling cascade plays a critical role in the initiation and development of dependence. Thus, phosphodiesterase 4 (PDE4), the primary hydrolytic enzyme for intracellular cAMP, is considered a potential target for future therapeutics dealing with prevention and intervention of substance dependence. This implication is supported by recent data from preclinical studies, and the rapid development of PDE4 inhibitors. Taken together, specific inhibitors of PDE4 and its subtypes possibly represent a novel class of pharmacotherapies for the prevention and abstinence of substance dependence. Here we discuss the modulatory role of cAMP signal transduction in the process of substance dependence and highlight recent evidence that PDE4 inhibitors might be a promising approach to substance dependence therapy.
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PMID:Role of phosphodiesterase 4-mediated cyclic AMP signaling in pharmacotherapy for substance dependence. 2515 74

Substance dependence is a chronic relapsing brain disorder associated with adaptational changes in synaptic plasticity and neuronal functions. The high levels of substance consumption and relapse rate suggest more reliable medications are in need to better address the underlying causes of this disease. It has been well established that the intracellular second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP) and their signaling systems play an important role in the molecular mechanisms of substance taking behaviors. On this basis, the phosphodiesterase (PDE) superfamily, which crucially controls cyclic nucleotide levels by catalyzing their hydrolysis, has been proposed as a novel class of therapeutic targets for substance use disorders. This chapter reviews the expression patterns of PDEs in the brain with regard to neural structures underlying the dependent process and highlights available evidence for a modulatory role of PDEs in substance dependence.
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PMID:Targeting Phosphodiesterases in Pharmacotherapy for Substance Dependence. 2895 41