scholarly journals OV329, a novel highly potent γ‐aminobutyric acid aminotransferase inactivator, induces pronounced anticonvulsant effects in the pentylenetetrazole seizure threshold test and in amygdala‐kindled rats

Epilepsia ◽  
2021 ◽  
Author(s):  
Malte Feja ◽  
Sebastian Meller ◽  
Lillian S. Deking ◽  
Edith Kaczmarek ◽  
Matthew J. During ◽  
...  
Keyword(s):  
Aminobutyric Acid ◽  
Seizure Threshold ◽  
Threshold Test ◽  
Anticonvulsant Effects

Effects of propofol and thiopentone on picrotoxin convulsive threshold in the rabbit

1995 ◽  
Vol 73 (6) ◽  
pp. 714-717 ◽  
Author(s):  
Zyheir Hasan ◽  
Said Khatib ◽  
Ayman Abu-Laban
Keyword(s):  
Intravenous Administration ◽  
Seizure Threshold ◽  
Intravenous Anesthetics ◽  
Threshold Test ◽  
Dose Dependent Increase ◽  
Convulsive Threshold ◽  
Dose Dependent ◽  
Higher Doses

The purpose of the present study was to examine the effect of intravenous administration of propofol and thiopentone on picrotoxin-induced seizures using the picrotoxin convulsive threshold test in the rabbit. Neither propofol nor thiopentone at a dose of 1.25 mg/kg had any significant effect on picrotoxin seizure threshold. However, at higher doses (2.5, 5, 10 mg/kg) both propofol and thiopentone produced a significant and dose-dependent increase in the picrotoxin convulsive threshold. These findings suggest that propofol is an effective anticonvulsant against picrotoxin-induced seizures in the rabbit.Key words: convulsions, intravenous anesthetics, picrotoxin, propofol, thiopentone.

scholarly journals Long-term vigabatrin treatment modifies pentylenetetrazole-induced seizures in mice: focused on GABA brain concentration

2019 ◽  
Vol 72 (2) ◽  
pp. 322-330
Author(s):  
Mariusz J. Świąder ◽  
Katarzyna Świąder ◽  
Izabela Zakrocka ◽  
Maciej Krzyżanowski ◽  
Andrzej Wróbel ◽  
...  
Keyword(s):  
Aminobutyric Acid ◽  
Seizure Threshold ◽  
Long Term Memory ◽  
Anticonvulsive Activity ◽  
Gaba Concentration ◽  
Term Memory ◽  
Long Term Effect ◽  
Brain Gaba ◽  
Gad Activity

Abstract Background The goal of our study was to examine the long-term effect of vigabatrin (VGB), a γ-aminobutyric acid aminotransferase (GABA-AT) inhibitor on clonazepam (CLO), ethosuximide (ETX) and valproate (VPA) anticonvulsive activity against pentylenetetrazole (PTZ)-induced seizures in mice. Methods VGB was administered for 3 and 7 days. Convulsions were evoked by PTZ at its CD97 (99 mg/kg). The influence of CLO, ETX and VPA alone or in combination with VGB on motor performance and long-term memory was analyzed. γ-aminobutyric acid (GABA) concentration in mice brain and plasma as well as glutamate decarboxylase (GAD) activity was measured. Results After 3 days of treatment, VGB in doses up to 500 mg/kg increased PTZ-induced seizure threshold, whereas after 7 days VGB (at the dose of 125 mg/kg) inhibited clonic seizures in experimental mice. 7 days of VGB administration did not change the protective effect of CLO, ETX and VPA against PTZ-induced seizures. 7 days of VGB treatment at a subthreshold dose of 75 mg/kg decreased TD50 of ETX and CLO in the chimney test, but did not affect TD50 value for VPA. 7 days of VGB administration in combination with AEDs did not affect long-term memory in mice. VGB after 3 days or 7 days of administration increased brain GABA concentration. GAD activity was decreased after 3 and 7 days of VGB administration. Conclusions The presented results confirm anticonvulsive activity of VGB through GABA metabolism alteration and suggest care when combining VGB with ETX or CLO in the therapy.

Possible Involvement of Endogenous Opioids and Nitric Oxide in the Anticonvulsant Effect of Acute Chloroquine Treatment in Mice

2017 ◽  
Vol 41 (S1) ◽  
pp. S630-S630
Author(s):  
A. Abkhoo
Keyword(s):  
Nitric Oxide ◽  
Effective Dose ◽  
Clonic Seizure ◽  
Endogenous Opioids ◽  
Seizure Threshold ◽  
Anticonvulsant Effect ◽  
Nitric Oxide Signaling ◽  
Nos Inhibitor ◽  
Neuronal Nos ◽  
Anticonvulsant Effects

IntroductionChloroquine, a 4-aminoquinoline derivative, has long been used for the treatment of malaria and rheumatological disorders, including rheumatoid arthritis and systemic lupus erythematosus. Accumulating evidence now suggests potential use of chloroquine as a neuroprotectant. Studies have shown that nitric oxide (NO) pathway is involved in the chloroquine actions. Considering the fact that nitrergic neurotransmission plays a crucial role in the central nervous system functioning, in the present study we evaluated whether nitrergic system is involved in the anticonvulsant effects of chloroquine in a model of clonicseizure in mice.MethodsClonic seizure threshold was determined by infusion of pentylenetetrazole (PTZ, 0.5%) at a constant rate of 1 mL/min into the tail vein of male Swiss mice (23–29 g). Minimal dose of PTZ (mg/kg of mice weight) needed to induce clonicseizure was considered as an index of seizure threshold.ResultsChloroquine (5 mg/kg, acutely 30 min before test, intraperitoneally), i.p significantly increased the seizure threshold. Acute co-administration of a non-effective dose of the non-selective NO synthase (NOS) inhibitor, L-NAME (L-NG-Nitro-L-arginine methyl ester hydrochloride,5 mg/kg, i.p.) or the selective inhibitor of neuronal NOS, 7-NI (7-nitroindazole, 40 mg/kg, i.p.) with an effective dose of chloroquine (5 mg/kg) inhibited its anticonvulsant effects. Co-administration of a non-effective dose the selective inducible NOS inhibitor, aminoguanidine (100 mg/kg, i.p.) with chloroquine 5 mg/kg did not alter its anticonvulsant effects.ConclusionChloroquine increases the PTZ-induced clonic seizure threshold in mice. We demonstrated for the first time that nitric oxide signaling probably through neuronal NOS could be involved in the anticonvulsant effects of chloroquine in this model of seizure in mice.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

LMR‐101, a novel derivative of propofol, exhibits potent anticonvulsant effects and possibly interacts with a novel target on γ‐aminobutyric acid type A receptors

Epilepsia ◽  
2021 ◽  
Vol 62 (1) ◽  
pp. 238-249
Author(s):  
Yi Zhao ◽  
Long An ◽  
Shupan Guo ◽  
Xiaoxing Huang ◽  
Huajie Tian ◽  
...  
Keyword(s):  
Type A ◽  
Aminobutyric Acid ◽  
Acid Type ◽  
Novel Target ◽  
Anticonvulsant Effects

scholarly journals Chronic convection-enhanced muscimol delivery into the subthalamic nucleus produces transient anticonvulsant effects in an acute rat seizure model.

2020 ◽  
Author(s):  
Malte Feja ◽  
Lillian S. Deking ◽  
Manuela Gernert
Keyword(s):  
Adverse Effects ◽  
Subthalamic Nucleus ◽  
Seizure Threshold ◽  
Epileptic Focus ◽  
Anticonvulsant Effect ◽  
Continuous Administration ◽  
Gaba A ◽  
Seizure Model ◽  
Epilepsy Models ◽  
Anticonvulsant Effects

Aims : Intracerebral drug delivery is an emerging strategy for the treatment of refractory epilepsies. Recently, the GABA A receptor agonist muscimol was infused into the epileptic focus in drug-resistant epilepsy patients (Heiss et al. 2019 Neurosurgery). In seizure and epilepsy models in rats, muscimol has shown anticonvulsant potential when injected acutely into the subthalamic nucleus (STN). However, continuous administration would be required for the clinical setting. Thus, we hypothesized that chronic convection-enhanced muscimol delivery into the STN produces anticonvulsant effects in an acute rat seizure model. Methods : We examined the effects of intra-STN muscimol following a single microinjection (30 and 60 ng/250 nl) and during continuous administration via a microinfusion pump (60 and 600 ng/day over 3 weeks) on the seizure threshold of female Wistar Unilever rats. Timed intravenous pentylenetetrazole (PTZ) infusion was used as an acute seizure test particularly sensitive to GABA-potentiating manipulations. Results : Acute STN muscimol infusion significantly increased PTZ seizure thresholds compared to vehicle-injected animals. The anticonvulsant effect persisted in the first week during chronic STN inhibition and diminished in the second week, indicating tolerance. Low doses of muscimol were well tolerated and not associated with behavioral adverse effects (e.g., sedation, circling) observed after infusion of higher doses. Evaluation of the spatial distribution of BODIPY-labeled muscimol revealed behavioral adverse effects may be attributable to drug spread into adjacent regions of the STN. Conclusions : These results substantiate the STN as a key region in seizure control and indicate the potential of chronic targeted muscimol delivery for prolonged anticonvulsant effects.

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