Antiepileptic Drugs and Their Dual Mechanism of Action on Carbonic Anhydrase

Magheru, Calin; Magheru, Sorina; Coltâu, Marcela; Hoza, Anica; Moldovan, Corina; Sachelarie, Liliana; Grădinaru, Irina; Hurjui, Loredana Liliana; Marc, Felicia; Farcaș, Dorina Maria

doi:10.3390/jcm11092614

Cited by 9 publications

(5 citation statements)

References 31 publications

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“…Carbonic anhydrase 1 (CA1) is a zinc enzyme that has an important role in acid-base balance [21]. Fluctuation in carbonic anhydrase expression possibly induces glaucoma, hypertension, neuropathic pain, epilepsy, and cancer [22][23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Biomarkers for Group I Pulmonary Hypertension Based on Machine Learning and Bioinformatics Analysis

Cai

et al. 2023

IJMS

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A number of processes and pathways have been reported in the development of Group I pulmonary hypertension (Group I PAH); however, novel biomarkers need to be identified for a better diagnosis and management. We employed a robust rank aggregation (RRA) algorithm to shortlist the key differentially expressed genes (DEGs) between Group I PAH patients and controls. An optimal diagnostic model was obtained by comparing seven machine learning algorithms and was verified in an independent dataset. The functional roles of key DEGs and biomarkers were analyzed using various in silico methods. Finally, the biomarkers and a set of key candidates were experimentally validated using patient samples and a cell line model. A total of 48 key DEGs with preferable diagnostic value were identified. A gradient boosting decision tree algorithm was utilized to build a diagnostic model with three biomarkers, PBRM1, CA1, and TXLNG. An immune-cell infiltration analysis revealed significant differences in the relative abundances of seven immune cells between controls and PAH patients and a correlation with the biomarkers. Experimental validation confirmed the upregulation of the three biomarkers in Group I PAH patients. In conclusion, machine learning and a bioinformatics analysis along with experimental techniques identified PBRM1, CA1, and TXLNG as potential biomarkers for Group I PAH.

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Biomarkers for Group I Pulmonary Hypertension Based on Machine Learning and Bioinformatics Analysis

Cai

et al. 2023

IJMS

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“…The negative control group received only the vehicle, water, and propylene glycol. Two positive control groups receiving 2 mg/kg of diazepam and 15 mg/kg of phenobarbital were used as reference anticonvulsants, in doses according to literature [20,37], chosen due to their mechanism of action, which targets both the GABA A receptor [38][39][40][41] and carbonic anhydrase II [42][43][44][45].…”

Section: Pentylenetetrazole (Ptz)-induced Seizuresmentioning

confidence: 99%

Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-One Derivatives

Pele,

Marc,

Mogoșan

et al. 2024

Molecules

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Two series, “a” and “b”, each consisting of nine chemical compounds, with 2,3-disubstituted quinazolin-4(3H)-one scaffold, were synthesized and evaluated for their anticonvulsant activity. They were investigated as dual potential positive allosteric modulators of the GABAA receptor at the benzodiazepine binding site and inhibitors of carbonic anhydrase II. Quinazolin-4(3H)-one derivatives were evaluated in vivo (D1–3 = 50, 100, 150 mg/kg, administered intraperitoneally) using the pentylenetetrazole (PTZ)-induced seizure model in mice, with phenobarbital and diazepam, as reference anticonvulsant agents. The in silico studies suggested the compounds act as anticonvulsants by binding on the allosteric site of GABAA receptor and not by inhibiting the carbonic anhydrase II, because the ligands-carbonic anhydrase II predicted complexes were unstable in the molecular dynamics simulations. The mechanism targeting GABAA receptor was confirmed through the in vivo flumazenil antagonism assay. The pentylenetetrazole experimental anticonvulsant model indicated that the tested compounds, 1a–9a and 1b–9b, present a potential anticonvulsant activity. The evaluation, considering the percentage of protection against PTZ, latency until the onset of the first seizure, and reduction in the number of seizures, revealed more favorable results for the “b” series, particularly for compound 8b.

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“…This is due to the fact that the medications that are currently available inhibit seizures. Due to the requirement for long-term therapy and the side effects of many medications, medication compliance is a significant issue [2].…”

Section: Introductionmentioning

confidence: 99%

Quality of life, adherence and knowledge of epileptic patients and the impact of a pharmacist‐led educational intervention: A review

Munaf,

Mohammed

2024

Medicine Advances

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Around 65 million individuals suffer from epilepsy worldwide, and when it is not properly treated, it is linked to higher rates of physical harm and mortality. Due to the requirement for long‐term therapy and the side effects of many medications, medication compliance is a significant issue. The purpose of this review was to summarize the findings of previous studies examining the quality of life (QOL), adherence, patient education, and medication knowledge, as well as the impact of a pharmacist‐led educational intervention. Additionally, to find out if these studies benefit epileptic patients, to find the appropriate method used to help them in all aspects of their lives, and to use these in future studies. A systematic and comprehensive search was conducted using specific keywords from PubMed, Google Scholar, and Research Gate. A significantly poorer QOL was linked to prolonged antiepileptic drug use or poor adherence as well as psychiatric problems. Neglect was the most frequent reason for nonadherence. The frequency of seizures was greatly reduced, and the adherence was significantly increased by patient education and medication understanding. Patient awareness, adherence, QOL, and seizure frequency were dramatically improved following the intervention. In the absence of optimal treatment, epilepsy is associated with increased rates of bodily injuries and mortality. It is crucial to increase patient education and knowledge about disease and treatment in order to improve adherence, and QOL. Intervention by a chemist is required to achieve these results.

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Antiepileptic Drugs and Their Dual Mechanism of Action on Carbonic Anhydrase

Cited by 9 publications

References 31 publications

Identification of Potential Biomarkers for Group I Pulmonary Hypertension Based on Machine Learning and Bioinformatics Analysis

Identification of Potential Biomarkers for Group I Pulmonary Hypertension Based on Machine Learning and Bioinformatics Analysis

Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-One Derivatives

Quality of life, adherence and knowledge of epileptic patients and the impact of a pharmacist‐led educational intervention: A review

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