The possibility of adverse effect of Kv7-channel opener retigabine on memory processes in rats

Zwierzyńska, Ewa; Krupa-Burtnik, Agata; Pietrzak, Bogusława

doi:10.1016/j.yebeh.2017.08.004

Cited by 5 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors suggested that this beneficial effect may be associated with regulating enzyme ubiquitin-specific proteases 2 (USP2)-related signaling pathways in hippocampal CA1 area [19]. However, in our previous study, retigabine administered as a single dose (20 mg/kg ig) or repeatedly (10 mg/kg ig), transiently disturbed learning processes in the MWM and passive avoidance test in rats [16].…”

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

Beneficial effect of retigabine on memory in rats receiving ethanol

2020

Self Cite

View full text Add to dashboard Cite

Background Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol. Methods Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation. Results The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. Conclusions This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction.

show abstract

Section: Discussionmentioning

confidence: 84%

“…The effect of retigabine administered alone on memory processes was assessed in MWM in our earlier study [16]. In the CFC and CuFC, the drug was administered together with ethanol for 3 weeks and also in the fourth week (without alcohol) only to two groups (RTG/ET_3W + RTG_4W).…”

Section: Drugsmentioning

confidence: 99%

Beneficial effect of retigabine on memory in rats receiving ethanol

2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Functional studies in heterologous expression systems revealed that mutations in KCNQ2 (and KCNQ3) genes are related to the onset of diseases such as epilepsy, benign familial neonatal convulsions (BFNC) or neonatal epileptic encephalopathy ( Miceli et al, 2013 ), peripheral nerve hyperexcitability (PNH or myokymia or neuromyotonia) ( Maljevic et al, 2008 ), neuropathic pain ( Di Cesare Mannelli et al, 2017 ), osteoarthritis or cancer pain, migraine, anxiety, dystonia and dyskinesia, bipolar disorder, bladder hypersensitive disorder, addiction, sensory deficits, stroke ( Miceli et al, 2008 ; Zwierzyńska et al, 2017 ; Du et al, 2018 ), mania ( Kristensen et al, 2012 ) and tinnitus ( Li et al, 2013 ). These channels were early identified as pharmacological targets, and M-channel enhancers such as retigabine (hereafter RTG) were developed and approved in humans [with indications and antiepileptic drug ( Brown and Passmore, 2009 )].…”

Section: Introductionmentioning

confidence: 99%

Molecular Insights Into Binding and Activation of the Human KCNQ2 Channel by Retigabine

Garofalo

Bonvin

Bosin

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Voltage-gated potassium channels of the Kv7.x family are involved in a plethora of biological processes across many tissues in animals, and their misfunctioning could lead to several pathologies ranging from diseases caused by neuronal hyperexcitability, such as epilepsy, or traumatic injuries and painful diabetic neuropathy to autoimmune disorders. Among the members of this family, the Kv7.2 channel can form hetero-tetramers together with Kv7.3, forming the so-called M-channels, which are primary regulators of intrinsic electrical properties of neurons and of their responsiveness to synaptic inputs. Here, prompted by the similarity between the M-current and that in Kv7.2 alone, we perform a computational-based characterization of this channel in its different conformational states and in complex with the modulator retigabine. After validation of the structural models of the channel by comparison with experimental data, we investigate the effect of retigabine binding on the two extreme states of Kv7.2 (resting-closed and activated-open). Our results suggest that binding, so far structurally characterized only in the intermediate activated-closed state, is possible also in the other two functional states. Moreover, we show that some effects of this binding, such as increased flexibility of voltage sensing domains and propensity of the pore for open conformations, are virtually independent on the conformational state of the protein. Overall, our results provide new structural and dynamic insights into the functioning and the modulation of Kv7.2 and related channels.

show abstract