scholarly journals Low-dose digoxin enhances the anticonvulsive potential of carbamazepine and lamotrigine in chemo-induced seizures with different neurochemical mechanisms

2021 ◽  
pp. 58-65
Author(s):  
Ihnat Havrylov ◽  
Vadim Tsyvunin ◽  
Sergiy Shtrygol’ ◽  
Diana Shtrygol’
Keyword(s):  
Antiepileptic Drugs ◽  
Low Dose ◽  
Multidrug Resistant ◽  
High Potential ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Low Doses ◽  
Neurochemical Mechanisms ◽  
Epilepsy Treatment ◽  
Mechanisms Of Development

"Non-antiepileptic" drugs have a strong potential as adjuvants in multidrug-resistant epilepsy treatment. In previous study the influence of low doses of digoxin, which do not affect the myocardium, on the anticonvulsant potential of classical commonly used anti-epileptic drugs under conditions of seizures, induced by pentylenetetrazole and maximal electroshock, has been investigated. The aim of the study was to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant potential of carbamazepine and lamotrigine in experimental seizures with different neurochemical mechanisms. Material and methods: A total of 192 random-bred male albino mice weighting 22–25 g were used. Carbamazepine and lamotrigine were administered intragastrically in conditionally effective (ED50) and sub-effective (½ ED50) doses: carbamazepine at doses of 100 and 50 mg/kg; lamotrigine at doses of 25 and 12.5 mg/kg. Digoxin was administered subcutaneously at a sub-cardiotonic dose of 0.8 mg/kg as an adjuvant to carbamazepine and lamotrigine in ½ ED50. Picrotoxin (2.5 mg/kg subcutaneously); thiosemicarbazide (25 mg/kg intraperitoneally); strychnine (1.2 mg/kg subcutaneously); camphor (1000 mg/kg intraperitoneally) were used as convulsant agents. Results: It was found that digoxin not only has its own permanent anticonvulsant effect on different models of paroxysms with different neurochemical mechanisms of development, but also significantly enhances the anticonvulsant potential of carbamazepine (to a lesser extent – lamotrigine) regardless of the pathogenesis of experimental paroxysms. Conclusion: Based on the results, it can be concluded that digoxin has a high potential as an adjuvant medicine in complex epilepsy treatment because it enhances the efficiency of low-dose traditional anticonvulsants carbamazepine and lamotrigine

Cholecalciferol enhances the anticonvulsant effect of conventional antiepileptic drugs in the mouse model of maximal electroshock

2007 ◽  
Vol 573 (1-3) ◽  
pp. 111-115 ◽  
Author(s):  
Kinga K. Borowicz ◽  
Marta Morawska ◽  
Kamila Furmanek-Karwowska ◽  
Jarogniew J. Luszczki ◽  
Stanislaw J. Czuczwar
Keyword(s):  
Mouse Model ◽  
Antiepileptic Drugs ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock

scholarly journals Combined anticonvulsant effect of nifedipine and pentazocine in experimentally induced seizures in rats

2019 ◽  
Vol 8 (8) ◽  
pp. 1875
Author(s):  
Santosh K. Banjara ◽  
Balakrishna Namala ◽  
Rajanna Ajumeera
Keyword(s):  
Antiepileptic Drugs ◽  
Hind Limb ◽  
Therapeutic Potential ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Medical College ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Post Hoc

Background: Epilepsy is one of the common disorders of human with a prevalence of approximately 1% of the total population. Majority of seizures can be controlled with available antiepileptic drugs, about 20% of them still remain resistant to treatment. Recognizing this, there is a need to develop newer antiepileptic drugs with therapeutic potential. Present work is based upon the production of convulsions by maximal electroshock in rats. Evaluation of combined anticonvulsant effect of nifedipine and pentazocine on the duration of convulsion and duration of tonic hind limb extension and recovery in rats.Methods: The study was commenced after obtaining approval from IAEC, Department of Pharmacology, Osmania Medical College, Koti, Hyderabad. All the wistar rats were induced convulsions by Maximal Electro-Shock (MES) method and rats showing tonic hind limb extension response were randomised into four groups (six animals in each group). Group 1 received distilled water, group 2 treated with nifedipine 10mg/kg BW, group 3 treated with pentazocine 30mg/kg BW and group 4 treated with both nifedipine 10mg/kg BW and pentazocine 30mg/kg BW. Drug administered by intraperitoneal route. The data analysed using ANOVA and group means with LSD Post Hoc Test. p‐values <0.05 were considered as significant.Results: When nifedipine and pentazocine were combined, the mean duration of convulsions, tonic hind limb extension and recovery were significantly decreased compared to control, nifedipine and pentazocine.Conclusions: The results obtained in this study provide supporting pharmacological evidence of efficacy, possible potential benefit of combining nifedipine with pentazocine in epilepsy.

scholarly journals Evaluation of anticonvulsant activity of amlodipine in albino rats

2017 ◽  
Vol 6 (3) ◽  
pp. 664
Author(s):  
Roopa B. ◽  
Janardhan M. ◽  
Venkata Rao Y.
Keyword(s):  
Experimental Animal ◽  
Anticonvulsant Activity ◽  
Low Dose ◽  
Combination Group ◽  
Albino Rats ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Standard Drug ◽  
Dose Dependent ◽  
Electroshock Seizures

Background: The objective of the study was to evaluate the anticonvulsant activity of amlodipine in albino rats.Methods: Anticonvulsant activity of amlodipine was done in three graded doses (1 mg/kg, 2 mg/kg, 4 mg/kg), and combination group with low dose of amlodipine (1 mg/kg) and standard drug (phenytoin) in maximal electroshock seizures (MES) experimental animal model.Results: Amlodipine in dose of 2, 4 mg/kg showed dose dependent significant anticonvulsant effect and combination of low dose amlodipine and low dose of standard drug also showed significant anticonvulsant effect in MES model.Conclusions: Amlodipine is having anticonvulsant activity and also potentiated the anticonvulsant effect of phenytoin in MES model. 

Verapamil enhances the anticonvulsant effect of oxcarbazepine in the maximal electroshock-induced seizure model in mice

2009 ◽  
Vol 22 (2) ◽  
pp. 115-124
Author(s):  
Anna Zadrożniak ◽  
MichaŁ K. Trojnar ◽  
Marcin P. Trojnar ◽  
Żaneta Kimber-Trojnar ◽  
Monika Dudra-Jastrzębska ◽  
...  
Keyword(s):  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Seizure Model

Potential anticonvulsants: Substituted N-benzylidene derivatives of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins

1983 ◽  
Vol 48 (4) ◽  
pp. 1173-1186 ◽  
Author(s):  
Václav Bártl ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Marie Bartošová ◽  
Miroslav Protiva
Keyword(s):  
Acute Toxicity ◽  
Water Soluble ◽  
Hypotensive Activity ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Soluble Salts ◽  
Sleeping Time ◽  
Central Depression ◽  
Derivatives Of ◽  
Electroshock Seizures

Reactions of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins XIVa-XIVd with benzaldehyde, 3,4-dimethoxybenzaldehyde, 4-dimethylaminobenzaldehyde, salicylaldehyde, 3-ethoxy-4-hydroxybenzaldehyde, 2-(2-dimethylaminoethoxy)benzaldehyde, 3-(2-dimethylaminoethoxy)benzaldehyde and 3-ethoxy-4-(2-dimethylaminoethoxy)benzaldehyde afforded a series of 19 hydrazones IIIa-Xc. Some of them showed the expected anticonvulsant effect but only towards pentetrazole; antagonism of maximal electroshock seizures was not observed. In general, the products have a character of tranquillizers: in higher does they produce central depression, potentiate the thiopental sleeping time, have hypothermic action; in single cases antiamphetamine, antireserpine, antihistamine and cataleptic effects were observed. The water-soluble salts of the basic hydrazones VIIIa, VIIIc, IXc and Xc, administered parenterally, showed a rather high acute toxicity and revealed also adrenolytic and hypotensive activity.

scholarly journals AB1335-HPR HEALTH PROFESSIONALS’ PERSPECTIVE ON THE BENEFITS AND RISKS OF LOW-DOSE GLUCOCORTICOIDS IN RHEUMATOID ARTHRITIS – AN INTERNATIONAL SURVEY OF 444 HEALTH PROFESSIONALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1955.1-1956
Author(s):  
T. Santiago ◽  
M. Voshaar ◽  
M. De Wit ◽  
P. Carvalho ◽  
M. Boers ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Health Professionals ◽  
Patient Perspective ◽  
Online Survey ◽  
Low Dose ◽  
Low Doses ◽  
Research Support ◽  
Serious Adverse Events ◽  
Patient Organizations

Background:The Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis Study (GLORIA) is an international investigator-initiated pragmatic randomized trial designed to study the effects of low-dose glucocorticoids (GCs) in elderly patients with Rheumatoid Arthritis (RA).The research team is also committed to promote a better understanding of the risks and benefits of these drugs among health professionals and patients. In order to achieve these goals, it is important to assess the current ideas and concerns of patients regarding GCs.Objectives:To evaluate the current patient perspective on the efficacy and risks of GCs in RA patients who are or have been treated with GCs.Methods:Patients with RA completed an online survey (with 5 closed questions regarding efficacy and safety) presented in their native language. RA patients were recruited through a variety of patient organizations representing three continents. Patients were invited to participate through national patient organizations. In the USA, patients were also invited to participate through MediGuard.org. Participants were asked for their level of agreement on a 5-point Likert scale.Results:1344 RA patients with exposure to GCs, from Brazil, USA, UK, Portugal, Netherlands, Germany and 24 other countries** participated: 89% female, mean age (SD) 52 (14) years and mean disease duration 13 (11) years. The majority of participants (84%) had ≥10 years of education. The duration of GCs exposure was 1.6 (4.2) years. The majority of participants had read articles or pamphlets on the benefits or harms of GC therapy.Regarding GCs efficacy (table 1), high levels of endorsement were found: about 2/3 of patients considered that GCs as very useful in their case, more than half considered that GCs were effective even at low doses, and agreed that GC improved RA symptoms within days.Regarding safety (table 1), 1/3 of the participants reported having suffered some form of serious adverse events (AEs) due to GCs, and 9% perceived this as “life-threatening. Adverse events had a serious impact on quality of life, according to about 1/3 of the respondents.Conclusion:Patients with RA exposed to GC report a strong conviction that GCs are very useful and effective for the treatment of their RA, even at low doses. This is accompanied by an important prevalence of serious AEs. Understanding the patient perspective can improve shared decision-making between patient and rheumatologist.Funding statement:This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634886.Disclosure of Interests:Tânia Santiago: None declared, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Maarten de Wit Grant/research support from: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Consultant of: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Speakers bureau: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Pedro Carvalho: None declared, Maarten Boers: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi., José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis

scholarly journals Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice

2021 ◽  
Author(s):  
Kinga K. Borowicz-Reutt ◽  
Monika Banach ◽  
Monika Rudkowska ◽  
Anna Stachniuk
Keyword(s):  
Antiepileptic Drugs ◽  
Second Generation ◽  
Antidepressant Drug ◽  
Experimental Models ◽  
Long Term Memory ◽  
Avoidance Task ◽  
Maximal Electroshock ◽  
Term Memory ◽  
The Brain

Abstract Background Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice. Materials and methods As a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay, while those of sotalol by liquid chromatography–mass spectrometry. Results Sotalol at doses of up to 100 mg/kg did not affect the electroconvulsive threshold. Applied at doses of 80–100 mg/kg, sotalol did not affect the antielectroshock action of oxcarbazepine, lamotrigine, pregabalin, or topiramate. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory. Finally, sotalol significantly decreased the brain concentrations of lamotrigine and increased those of oxcarbazepine and topiramate. Pharmacokinetic interactions, however, did not influence the final antielectroshock effects of above-mentioned drug combinations. On the other hand, the brain concentrations of sotalol were not changed by second-generation antiepileptics used in this study. Conclusion Sotalol did not reduce the antielectroshock action of four second-generation antiepileptic drugs examined in this study. Therefore, this antidepressant drug should not interfere with antiseizure effects of lamotrigine, oxcarbazepine, pregabalin, and topiramate in patients with epilepsy. To draw final conclusions, our preclinical data should still be confirmed in other experimental models and clinical conditions.

scholarly journals Sorafenib is a potent inhibitor of FIP1L1-PDGFRα and the imatinib-resistant FIP1L1-PDGFRα T674I mutant

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1374-1376 ◽  
Author(s):  
Els Lierman ◽  
Cedric Folens ◽  
Elizabeth H. Stover ◽  
Nicole Mentens ◽  
Helen Van Miegroet ◽  
...  
Keyword(s):  
Low Dose ◽  
Potent Inhibitor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Low Doses ◽  
Chronic Eosinophilic Leukemia ◽  
Nanomolar Concentration ◽  
Imatinib Resistant ◽  
Factor Receptor Alpha ◽  
Induced Apoptosis

Abstract The FIP1L1-PDGFRA oncogene is a common cause of chronic eosinophilic leukemia (CEL), and encodes an activated tyrosine kinase that is inhibited by imatinib. FIP1L1-PDGFRA–positive patients with CEL respond to low-dose imatinib therapy, but resistance due to acquired T674I mutation has been observed. We report here the identification of sorafenib as a potent inhibitor of the FIP1 like 1–platelet-derived growth factor receptor alpha (FIP1L1-PDGFRα) (T674I) mutant. Sorafenib inhibited the proliferation of FIP1L1-PDGFRα and FIP1L1-PDGFRα(T674I)–transformed Ba/F3 cells and induced apoptosis of the EOL-1 cell line at a low nanomolar concentration. Western blot analysis confirmed that these effects were due to a direct effect on FIP1L1-PDGFRα and FIP1L1-PDGFRα(T674I). Sorafenib was recently approved for the treatment of renal cell carcinoma. Our data suggest that low doses of sorafenib could be efficient for the treatment of FIP1L1-PDGFRA–positive CEL and could be used to overcome resistance to imatinib associated with the T674I mutation.

scholarly journals How Antidepressant Drugs Affect the Antielectroshock Action of Antiseizure Drugs in Mice: A Critical Review

2021 ◽  
Vol 22 (5) ◽  
pp. 2521
Author(s):  
Kinga K. Borowicz-Reutt
Keyword(s):  
Antiepileptic Drugs ◽  
Neurotrophic Factor ◽  
Antidepressant Drugs ◽  
Drug Effects ◽  
Mechanisms Of Action ◽  
Maximal Electroshock ◽  
Anticonvulsant Action ◽  
Mes Test ◽  
Seizure Model ◽  
Glial Derived Neurotrophic Factor

Depression coexists with epilepsy, worsening its course. Treatment of the two diseases enables the possibility of interactions between antidepressant and antiepileptic drugs. The aim of this review was to analyze such interactions in one animal seizure model—the maximal electroshock (MES) in mice. Although numerous antidepressants showed an anticonvulsant action, mianserin exhibited a proconvulsant effect against electroconvulsions. In most cases, antidepressants potentiated or remained ineffective in relation to the antielectroshock action of classical antiepileptic drugs. However, mianserin and trazodone reduced the action of valproate, phenytoin, and carbamazepine against the MES test. Antiseizure drug effects were potentiated by all groups of antidepressants independently of their mechanisms of action. Therefore, other factors, including brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) modulation, should be considered as the background for the effect of drug combinations.

Thiamme2-G, A Novel O-GlcNAcase Inhibitor, Reduces Tau Hyperphosphorylation and Rescues Cognitive Impairment in Mice

2021 ◽  
pp. 1-14
Author(s):  
Danmin Pan ◽  
Jin-Hua Gu ◽  
Jin Zhang ◽  
Yae Hu ◽  
Fei Liu ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Low Dose ◽  
Body Weight Loss ◽  
Synaptic Proteins ◽  
Novel Object Recognition ◽  
Low Doses ◽  
Tau Hyperphosphorylation ◽  
Protein Tau ◽  
Abnormal Hyperphosphorylation ◽  
Brain Changes

Background: Abnormal hyperphosphorylation of microtubule-associated protein tau plays a pivotal role in Alzheimer’s disease (AD). We previously found that O-GlcNAcylation inversely correlates to hyperphosphorylation of tau in AD brain, and downregulation of brain O-GlcNAcylation promotes tau hyperphosphorylation and AD-like neurodegeneration in mice. Objective: Herein we investigated the effect of increasing O-GlcNAcylation by using intermittent dosing with low doses of a potent novel O-GlcNAcase (OGA) inhibitor on AD-like brain changes and cognitive function in a mouse model of sporadic AD (sAD) induced by intracerebroventricular (ICV) injection of streptozotocin (STZ). Methods: STZ was injected into the lateral ventricle of C57BL/6J mice. From the second day, Thiamme2-G (TM2G) or saline, as a vehicle control, was orally administered to the ICV-STZ mice three times per week for five weeks. A separate group of ICV-saline mice treated with saline was used as a baseline control. Behavioral tests, including open field and novel object recognition, were conducted three weeks after the first dose of the TM2G or saline. Protein O-GlcNAcylation, tau hyperphosphorylation, synaptic proteins, and neuroinflammation in the mouse brain were assessed by western blotting. Results: ICV-STZ caused decreased protein O-GlcNAcylation. Enhancement of O-GlcNAcylation to moderate levels by using low-dose OGA inhibitor in ICV-STZ mice prevented STZ-induced body weight loss, rescued cognitive impairments, and restored AD-like pathologies, including hyperphosphorylation of tau and abnormalities in synaptic proteins and neuroinflammation. Conclusion: These findings suggest that moderately increasing protein O-GlcNAcylation by using low doses of OGA inhibitor may be a suitable therapeutic strategy for sAD.

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