Assessment of drug‐drug interactions between moxonidine and antiepileptic drugs in the maximal electroshock seizure test in mice

2021 ◽  
Author(s):  
Krzysztof Łukawski ◽  
Stanisław Jerzy Czuczwar
Keyword(s):  
Drug Interactions ◽  
Antiepileptic Drugs ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Maximal Electroshock Seizure Test

scholarly journals Syntheses of Benzo[d]Thiazol-2(3H)-One Derivatives and Their Antidepressant and Anticonvulsant Effects

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 430 ◽  
Author(s):  
Qinghao Jin ◽  
Zhiyang Fu ◽  
Liping Guan ◽  
Haiying Jiang
Keyword(s):  
Forced Swimming Test ◽  
Antidepressant Activity ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Immobility Duration ◽  
Maximal Electroshock Seizure Test ◽  
Percentage Decrease ◽  
Swimming Test ◽  
Anticonvulsant Effects

Thirty-four new benzo[d]thiazol derivatives 2a–2i, 3a–3r, and 4a–4g were synthesized and investigated for their potential antidepressant and anticonvulsant effects. In a forced swimming test, 2c and 2d showed the highest antidepressant and anticonvulsant effects. 2c and 2d displayed a higher percentage decrease in immobility duration (89.96% and 89.62%, respectively) than that of fluoxetine (83.62%). In the maximal electroshock seizure test, 3n and 3q showed the highest anticonvulsant effect, with ED50 values of 46.1 and 64.3 mg kg−1, and protective indices of 6.34 and 4.11, respectively, which were similar to those of phenobarbital or valproate. We also found that the mechanism for the antidepressant activity of 2c and 2d may be via increasing the concentrations of serotonin and norepinephrine.

Synthesis and Anticonvulsant Activity of α-Amino Acid Amide Derivatives

2019 ◽  
Vol 15 (5) ◽  
pp. 547-561
Author(s):  
Valerie Currier ◽  
Maryam Molki ◽  
Katelyn Fryman ◽  
Lacey D. Rodgers ◽  
A. Michael Crider
Keyword(s):  
Amino Acid ◽  
Side Effects ◽  
Anticonvulsant Activity ◽  
Acid Amide ◽  
New Drugs ◽  
Seizure Threshold ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Maximal Electroshock Seizure Test ◽  
Amide Derivatives

Background: Epilepsy is a disease of the central nervous system that affects approximately 50 million individuals worldwide. Although several new drugs have been marketed in the last 25 years, almost one-third of patients are not protected. In many cases, currently available drugs produce undesirable side effects. As a result, a need exists for novel anticonvulsants with unique mechanisms of action and minimal side effects. Methods: A mixed anhydride coupling procedure and standard deprotection procedures were utilized to prepare 36 α-amino acid amides. All final products were evaluated in mice and rats utilizing a standard battery of anticonvulsant tests. Results: α-Amino acids containing a 2,6-dimethylanilide group exhibited anticonvulsant activity in the maximal electroshock seizure test and 6 Hz test in mice and rats. A small, branched-chain on the α- carbon generally maintained or enhanced anticonvulsant activity in the maximal electroshock seizure test. The (R)-α-amino acid amides were typically more potent and slightly more neurotoxic than the corresponding (S)-enantiomers. The valine dimethylanilide (R)-42 was highly active in the MES test in mice (ED50 = 3.6mg/kg) and rats (ED50 = 3.8 mg/kg). (R)-42 also demonstrated excellent anticonvulsant activity in the 6 Hz, picrotoxin, and corneal kindled mouse tests. Furthermore, (R)-42 did not lower seizure threshold when evaluated in the intravenous metrazol seizure test. Conclusion: α-Amino acid 2,6-dimethylanilides exhibited potent activity in a variety of anticonvulsant tests in mice and rats. The valine derivative (R)-42 represents a promising compound for potential use in complex partial seizures.

scholarly journals Polygonogram with isobolographic synergy for three-drug combinations of phenobarbital with second-generation antiepileptic drugs in the tonic–clonic seizure model in mice

2020 ◽  
Author(s):  
Jarogniew J. Łuszczki ◽  
Dominika Podgórska ◽  
Justyna Kozińska ◽  
Marek Jankiewicz ◽  
Zbigniew Plewa ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Antiepileptic Drugs ◽  
Second Generation ◽  
Drug Combinations ◽  
Maximal Electroshock ◽  
Type I ◽  
Swiss Mice ◽  
Total Brain ◽  
Seizure Model ◽  
The Impact

Abstract Background Combination therapy consisting of two or more antiepileptic drugs (AEDs) is usually prescribed for patients with refractory epilepsy. The drug–drug interactions, which may occur among currently available AEDs, are the principal criterion taken by physicians when prescribing the AED combination to the patients. Unfortunately, the number of possible three-drug combinations tremendously increases along with the clinical approval of novel AEDs. Aim To isobolographically characterize three-drug interactions of phenobarbital (PB) with lamotrigine (LTG), oxcarbazepine (OXC), pregabalin (PGB) and topiramate (TPM), the maximal electroshock-induced (MES) seizure model was used in male albino Swiss mice. Materials and method The MES-induced seizures in mice were generated by alternating current delivered via auricular electrodes. To classify interactions for 6 various three-drug combinations of AEDs (i.e., PB + TPM + PGB, PB + OXC + TPM, PB + LTG + TPM, PB + OXC + PGB, PB + LTG + PGB and PB + LTG + OXC), the type I isobolographic analysis was used. Total brain concentrations of PB were measured by fluorescent polarization immunoassay technique. Results The three-drug mixtures of PB + TPM + PGB, PB + OXC + TPM, PB + LTG + TPM, PB + OXC + PGB, PB + LTG + PGB and PB + LTG + OXC protected the male albino Swiss mice from MES-induced seizures. All the observed interactions in this seizure model were supra-additive (synergistic) (p < 0.001), except for the combination of PB + LTG + OXC, which was additive. It was unable to show the impact of the studied second-generation AEDs on total brain content of PB in mice. Conclusions The synergistic interactions among PB and LTG, OXC, PGB and TPM in the mouse MES model are worthy of being transferred to clinical trials, especially for the patients with drug resistant epilepsy, who would benefit these treatment options.

Amiloride enhances the anticonvulsant action of various antiepileptic drugs in the mouse maximal electroshock seizure model

2008 ◽  
Vol 116 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Jarogniew J. Luszczki ◽  
Katarzyna M. Sawicka ◽  
Justyna Kozinska ◽  
Monika Dudra-Jastrzebska ◽  
Stanislaw J. Czuczwar
Keyword(s):  
Antiepileptic Drugs ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Anticonvulsant Action ◽  
Seizure Model
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