Psychiatric aspects of phosphodiesterases: An overview

Murthy, Vasantmeghna S; Mangot, Ajish G

doi:10.4103/0253-7613.169593

Cited by 9 publications

(5 citation statements)

References 29 publications

(31 reference statements)

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“…More specifically, in the same neuron, cAMP compartmentalization and control of cyclic nucleotide levels within narrow ranges of concentrations are ensured by diverse PDE subtypes 57 . Hence, cyclic nucleotides play a key role in inter/intracellular communication in neurons and affect neurotransmission in psychiatric disorders 58 .…”

Section: Discussionmentioning

confidence: 99%

Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents

et al. 2019

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Phosphodiesterases (PDE) are key modulators of signal transduction and are involved in inflammatory cell activation, memory and cognition. There is a two-fold decrease in the expression of phosphodiesterase 8A (PDE8A) in the temporal cortex of major depressive disorder (MDD) patients. Here, we studied PDE8A mRNA-editing profile in two architectonically distinct neocortical regions in a clinically well-characterized cohort of age- and sex-matched non-psychiatric drug-free controls and depressed suicide decedents. By using capillary electrophoresis single-stranded conformational polymorphism (CE-SSCP), a previously validated technique to identify A-to-I RNA modifications, we report the full editing profile of PDE8A in the brain, including identification of two novel editing sites. Editing of PDE8A mRNA displayed clear regional difference when comparing dorsolateral prefrontal cortex (BA9) and anterior cingulate cortex (BA24). Furthermore, we report significant intra-regional differences between non-psychiatric control individuals and depressed suicide decedents, which could discriminate the two populations. Taken together, our results (i) highlight the importance of immune/inflammatory markers in major depressive disorder and suicide and (ii) establish a direct relationship between A-to-I RNA modifications of peripheral markers and A-to-I RNA editing-related modifications in brain. This work provides the first immune response-related brain marker for suicide and could pave the way for the identification of a blood-based biomarker that predicts suicidal behavior.

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Section: Discussionmentioning

confidence: 99%

Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents

et al. 2019

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“…Moreover, tofisopam is marketed in other international countries, such as Japan, India, Russia etc . [ 176 , 177 ]. Pellow et al .…”

Section: Resultsmentioning

confidence: 99%

“…Tofisopam has multiple selective phosphodiesterase (PDE)-inhibiting actions ( i.e . at PDE 4A1 , PDE 10A1 , PDE 3 and PDE 2A3 ) which are being actively evaluated for managing negative and cognitive symptoms of schizophrenia [ 176 , 180 , 183 , 184 ]. Furthermore, it does not impair psychomotor and intellectual performance, like other BZDs and it has a potent capability in alleviating vegetative symptoms accompanying anxiety disorders [ 182 , 185 - 188 ].…”

Section: Resultsmentioning

confidence: 99%

‘New/Designer Benzodiazepines’: An Analysis of the Literature and Psychonauts’ Trip Reports

Orsolini

Corkery

Chiappini

et al. 2020

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Background: NPS belonging to the benzodiazepine (BZD) class, e.g., ‘legal/designer BZDs’/‘research chemicals’, have recently emerged on the drug (mainly online/virtual) market. Objective: Whilst certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians’/public health knowledge/awareness, to incentive harm reduction strategies. Method: A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the ‘new BZDs’ so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/toxicological data, including psychonauts’ online trip reports. Results: First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds. Conclusions: Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.

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“…In contrast, it has a cognitive stimulatory activity. 16 The anti-amnesic effects of tofisopam, with concomitant improvements in hippocampal synaptogenesis, neurogenesis, and glial plasticity, have been found in animal studies. 17 Besides, tofisopam has been reported to have an antidepressant property, possibly by sharing a mechanism similar to Serotonin Norepinephrine Reuptake Inhibitors via phosphodiesterase 4 inhibition.…”

Section: Discussionmentioning

confidence: 98%

Role of Tofisopam in Post COVID Neuro-psychiatric Sequelae: A Case Series

Pattnaik

Deepthi

Dua

et al. 2021

Indian Journal of Psychological Medicine

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A 52-year-old businessman, with no contributory medical or neuropsychiatric comorbidities, was hospitalized for COVID-19 pneumonia. He received conservative management as per COVID-19 treatment guidelines and was discharged after a week. Within a week of the discharge, he reported being withdrawn, having decreased interaction with family members, remaining mute for hours together, hypersomnolence, and sometimes would not swallow the chewed food. He was brought to the psychiatric outpatient department for evaluation. On Mini Mental State Examination, he scored 24 out of 27. In the Bush Francis Catatonia Rating Scale, the score was 24, with higher scores in the domains of mutism, verbal fluency, and negativism. EEG and MRI brain were normal. In view of catatonia and recent recovery from COVID pneumonia, a benzodiazepine without respiratory suppression effect, tofisopam, was administered at a dose of 100 mg/per day, in divided doses, for two weeks. No respiratory

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Psychiatric aspects of phosphodiesterases: An overview

Cited by 9 publications

References 29 publications

Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents

Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents

‘New/Designer Benzodiazepines’: An Analysis of the Literature and Psychonauts’ Trip Reports

Role of Tofisopam in Post COVID Neuro-psychiatric Sequelae: A Case Series

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