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Effect of propranolol and nifedipine on maximal electroshock-induced seizures in mice: individually and in combination

Raju SS, Gopalakrishna HN, Venkatadri N

Pharmacol Res, 1998 Dec;38(6):449-52.
PMID: 9990653

A comparative effect of propranolol and nifedipine administered individually and in combination at graded dose levels; and that of phenytoin at 30 mg kg-1 on maximal electroshock (MES)-induced seizure in mice was investigated. Propranolol in doses of 10 mg kg-1 and 20 mg kg-1, and nifedipine in doses of 8 mg kg-1 and 16 mg kg-1 significantly modified MES activity. Propranolol (40 mg kg-1), and a combination of propranolol (20 mg kg-1) and nifedipine (8 mg kg-1), produced antiMES activity, which was comparable to that of phenytoin (30 mg kg-1). In mice treated with propranolol and nifedipine combination, the tonic flexor and tonic extensor phase ratios (F/E ratio) were significantly higher than individual drug responses. Our findings suggest that a combination of propranolol and nifedipine has either synergistic or an additive effect in controlling MES-induced seizures in mice.

Matched MeSH terms: Seizures/prevention & control*
Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial

Lamy A, Sirota DA, Jacques F, Poostizadeh A, Noiseux N, Efremov S, et al.

Circulation, 2024 Oct 22;150(17):1315-1323.
PMID: 38587333 DOI: 10.1161/CIRCULATIONAHA.124.069606

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients.
METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis, when 75% of anticipated participants had completed follow up, the data and safety monitoring board recommended to terminate the trial, and upon unblinding, the operations committee stopped the trial for safety.
RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group, and 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5% [95% CI, -0.9 to 0.03]; P=0.07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3% [95% CI, 5.2-11.5]; P=0.007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared with the intravenous group was 8.2% (95% CI, 3.4-12.9).
CONCLUSIONS: Among patients undergoing cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared with intravenous tranexamic acid.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03954314.

Matched MeSH terms: Seizures/prevention & control
Fulltext The quality of life of people with epilepsy at a tertiary referral centre in Malaysia

Norsa'adah B, Zainab J, Knight A

Health Qual Life Outcomes, 2013;11:143.
PMID: 23972031 DOI: 10.1186/1477-7525-11-143

Epilepsy, a chronic disorder of brain characterised by a predisposition to generate epileptic seizures, has an effect on the psychosocial well-being of sufferers. Measuring the quality of life (QOL) of people with epilepsy (PWE) is increasingly recognized as an important component of clinical management. QOL measures differ between countries and there is limited information regarding PWE in Malaysia. The aim of this study was to determine the health related QOL and its relationship with the presence of seizures in PWE at a Malaysian tertiary referral center.

Matched MeSH terms: Seizures/prevention & control
The use of lamotrigine and other antiepileptic drugs in paediatric patients at a Malaysian hospital

Ab Rahman AF, Ibrahim MI, Ismail HI, Seng TB

Pharm World Sci, 2005 Oct;27(5):403-6.
PMID: 16341748

OBJECTIVE: (1) To determine the effect of lamotrigine add-on therapy on the seizure frequency and cost in paediatric patients. (2) To determine the prescribing pattern of other antiepileptic drugs (AEDs).

METHOD: A retrospective study of medical records was carried out from October 2000 to June 2001 at the paediatric clinic, Hospital Pulau Pinang.

MAIN OUTCOME MEASURE: Seizure frequency, cost of drug and types of AED prescribed.

RESULTS: A total of 209 medical records were retrieved during the study period. Lamotrigine (LTG) was prescribed in 29 patients as add-on therapy. In 18 patients, there was a significant reduction in seizure frequency after the addition of LTG. Approximately 70% experienced a reduction in seizure frequency of more than 50%. Side effects of LTG were considered mild and manageable. However, drug cost after the addition of LTG increased by 103%. In the remaining 180 patients, the most common AED prescribed was sodium valproate (VPA). Only 15% of the patients received combination therapy. Mean monthly cost of monotherapy was found to be RM 24.4 while monthly cost of combination therapy was RM 45.4 (1 Euro-RM 5.00).

CONCLUSION: The majority of paediatric patients in the study are on AED monotherapy and only a small percentage was prescribed lamotrigine. The use of lamotrigine is associated with better seizure control but with an increase in drug cost.

Study site: paediatric clinic, Hospital Pulau Pinang.

Matched MeSH terms: Seizures/prevention & control
Refractory seizures in a young army cohort

Loh NK, Lee WL, Yew WW, Tjia TL

Ann Acad Med Singap, 1997 Jul;26(4):471-4.
PMID: 9395813

This survey covered male Singapore citizens born in 1974 who were medically screened at the age of 18 years before enlistment for compulsory military service. Suspected epileptics were referred to government hospitals for further management. Out of 20,542 men, there were 121 epileptics, giving a cumulative incidence of 5 per 1000 by age 18 years. We had information on 106 (87%) of these individuals and were able to interview them and review their hospital records. Seventy-three of the 106 (69%) epileptics had generalised seizures while 14 (13%) had refractory seizures. There was no statistically significant racial bias amongst these epileptics. Unprovoked afebrile seizures occurred early in these patients, half of whom had seizures onset before 7 years of age. Nine refractory epileptics had a history of febrile seizures, 4 of which were complex febrile seizures. Magnetic resonance imaging identified mesial temporal sclerosis in 2 patients and a hypothalamic lesion in 1 patient. Computed tomographic scans revealed focal cortical atrophy in 2 patients. Nine other patients had normal imaging studies. Nine out of 14 (64%) patients with refractory epilepsy had partial seizures; 4 (29%) had generalised seizures and 1 (7%) was unclassified. This is in contrast to the distribution of the entire cohort of epileptics studied. Two out of 9 patients with refractory partial seizures (gelastic epilepsy and mesial temporal sclerosis) had undergone surgery while 6 of the other 7 patients refused to consider surgery.

Matched MeSH terms: Seizures/prevention & control
Fulltext NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy

Rothan HA, Amini E, Faraj FL, Golpich M, Teoh TC, Gholami K, et al.

Sci Rep, 2017 03 30;7:45540.
PMID: 28358047 DOI: 10.1038/srep45540

N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants.

Matched MeSH terms: Seizures/prevention & control*
Fulltext Protective effect of α-asarone against nicotine-induced seizures in mice, but not by its interaction with nicotinic acetylcholine receptors

Chellian R, Pandy V

Biomed Pharmacother, 2018 Dec;108:1591-1595.
PMID: 30372861 DOI: 10.1016/j.biopha.2018.09.137

Alpha-asarone is one of the bioactive phytochemicals present in the rhizomes of Acorus species and demonstrated its anticonvulsant activity in rodents. Alpha-asarone protected mice from the gamma-aminobutyric acid (GABA) type A receptor antagonist or N-methyl-d-aspartate (NMDA) receptor agonist-induced seizures. In our recent study, α-asarone attenuated the nicotine withdrawal-induced depression-like behavior in mice. The seizures induced by nicotine is mediated through the activation of nicotinic acetylcholine receptors (nAChRs) and stimulation of NMDA receptors. Therefore, we hypothesized that α-asarone might be effective against nicotine-induced seizures. Also, the interaction of α-asarone with nAChRs is unknown. In this study, we investigated the effect of α-asarone on the locomotor activity and body temperature in mice. In addition, we studied the effect of α-asarone on nicotine-induced seizures in mice. Finally, we assessed in vivo pharmacodynamic interaction of α-asarone with nAChRs using nicotine-induced hypomotility and hypothermia tests in mice. The results of this study showed that the α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) treatment significantly decreased the locomotor activity and body temperature in mice. Furthermore, α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) pretreatment significantly prolonged the onset time of nicotine-induced seizures in mice. However, α-asarone (30 and 50 mg/kg, i.p.) pretreatment did not inhibit the nicotine-induced hypomotility or hypothermia in mice. Conversely, mecamylamine (1 mg/kg, s.c.) pretreatment completely blocked the nicotine-induced seizures and significantly prevents the nicotine-induced hypomotility and hypothermia in mice. Overall, these results suggest that the protective effect of α-asarone against nicotine-induced seizures did not mediate through the antagonism of nAChRs. We also postulated that the GABAergic and glutamatergic activities of α-asarone could be involved in its protective effect against nicotine-induced seizures and based on this aspect further studies are required.

Matched MeSH terms: Seizures/prevention & control*
Antibacterial, antifungal and anticonvulsant evaluation of novel newly synthesized 1-[2-(1H-tetrazol-5-yl)ethyl]-1H-benzo[d][1, 2,3]triazoles

Rajasekaran A, Murugesan S, AnandaRajagopal K

Arch Pharm Res, 2006 Jul;29(7):535-40.
PMID: 16903071

Several novel 1-[2-(1H-tetrazol-5-yl) ethyl]-1H-benzo[d][1,2,3]triazoles (3a-h) have been synthesized by the condensation of 1-[2-(1H-tetrazol-5-yl)-ethyl]-1H-benzotriazole (2) and appropriate acid chlorides. 1-[2-(1H-tetrazol-5-yl)-ethyl]-1H-benzotriazole (2) was synthesized by reacting 3-(1H-benzo[d][1,2,3]triazol-1-yl)propanenitrile with sodium azide and ammonium chloride in the presence of dimethylformamide. The synthesized compounds were characterized by IR and PMR analysis. The titled compounds were evaluated for their in-vitro antibacterial and antifungal activity by the cup plate method and anticonvulsant activity evaluated by the maximal electroshock induced convulsion method in mice. All synthesized compounds exhibited moderate antibacterial activity against Bacillus subtilis and moderate antifungal activity against Candida albicans. Compounds 5-(2-(1H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(4-aminophenyl)methanone 3d and 5-(2-(1 H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(2-aminophenyl)methanone 3e elicited excellent anticonvulsant activity.

Matched MeSH terms: Seizures/prevention & control