Effect of magnesium oxide on the activity of standard anti-epileptic drugs against experimental seizures in rats

Abstract

Objectives:To study the effect of oral magnesium oxide supplementation alone and on the activity of standard anti-epileptic drugs in the animal models of maximal electroshock seizures (MES) and chemically (pentylenetetrazole [PTZ])-induced seizures.Methods:Healthy male albino rats were given magnesium oxide (MgO) supplementation orally in various doses (500, 750 and 1000 mg/kg /day) for 4 weeks (day 1 to day 28). On day 0 and day 29, response to MES (180 mA for 0.2 s) was tested 1 h after pre-administration of phenytoin or carbamazepine orally. Similarly, in the other groups, the response to PTZ 40 mg/kg i.p. was tested 1 h after pre-administration of oral sodium valproate.Results:Oral administration of MgO in a low dose (500 mg/kg) for 4 weeks in healthy rats appears to exert protective effect against MES. High oral doses of MgO (750 and 1000 mg/kg) appear to enhance the activity of phenytoin and carbamazepine in the MES model. MgO supplementation was seen to decrease the latency of PTZ-induced seizures.Conclusion:The dose of oral MgO appears to have an inverse relation with the protective effect in MES-induced seizure model. High doses of MgO supplementation given orally appear to enhance the activity of standard anti-epileptic drugs in the MES-induced seizure model.

Brain protection by rapeseed oil in magnesium-deficient mice

“…Anticonvulsant properties of magnesium salts have been largely documented to be effective via diverse routes of administration in the human [20,38] and in the animals pre-supplied [39,40] or not [41] with a magnesium-deficient diet. Magnesium suppressive action on the NMDA receptor calcium channel complex results from a block in ion permeation, occurs in a voltage-dependent manner, and this effect has been supported to take place in vitro [42,43], ex vivo [44] and in vivo [22].…”

Carbamazepine Alleviates Retinal and Optic Nerve Neural Degeneration in Diabetic Mice via Nerve Growth Factor-Induced PI3K/Akt/mTOR Activation

“…In one study, mice were given a 50-mg/kg dose of CARB orally, daily for a couple of weeks (Chen and Ma, 2017). Another study tested the anticonvulsant effect of oral CARB in rats at 35 and 50 mg/kg (Dhande et al, 2009). Before the start of this study, a preliminary experiment was performed, in which mice were given 25 and 50 mg/kg CARB orally on 48 h basis; this schedule was fine and provided a promising retinoprotective effect, hence was used in the current study.…”

Addressing potential role of magnesium dyshomeostasis to improve treatment efficacy for epilepsy: A reexamination of the literature

“…Oral magnesium oxide (MgO) supplementation alone and in combination with standard antiepileptic drugs in 2 animal models of seizuremaximal electroshock seizures (MESs) and chemically (pentylenetetrazole [PTZ]) induced seizuresfound that chronic administration (4 weeks) of MgO had no significant effect on the latency of PTZ-induced seizures, but appeared to exert a protective effect against MESs at low doses and enhance the activity of phenytoin and carbamazepine in the MES model at higher doses. 58 Although magnesium citrate and an amino acid chelate of megnesium were found to have better oral bioavailability than inorganic MgO in a randomized double-blind study, 59 the antiseizure efficacy of MgO in diabetic mice was largely dependent on particle size, with nanoparticle MgO having higher efficacy over conventional MgO. 60 Although not discussed by the authors, a smaller particle size might explain why oral MgO treatment significantly increased intracellular Mg 2þ and lowered total and low-density lipoprotein cholesterol plasma levels when compared with oral magnesium citrate in healthy human subjects.…”

“…Several different salts (both organic and inorganic) and chelates of magnesium are available over the counter. Oral magnesium oxide (MgO) supplementation alone and in combination with standard antiepileptic drugs in 2 animal models of seizure — maximal electroshock seizures (MESs) and chemically (pentylenetetrazole [PTZ]) induced seizures — found that chronic administration (4 weeks) of MgO had no significant effect on the latency of PTZ‐induced seizures, but appeared to exert a protective effect against MESs at low doses and enhance the activity of phenytoin and carbamazepine in the MES model at higher doses . Although magnesium citrate and an amino acid chelate of megnesium were found to have better oral bioavailability than inorganic MgO in a randomized double‐blind study, the antiseizure efficacy of MgO in diabetic mice was largely dependent on particle size, with nanoparticle MgO having higher efficacy over conventional MgO .…”