A study of the effects of lamotrigine on mice using two convulsive tests

Abstract

AIm was to study the effects of lamotrigine on bicuculline and pentylenetetrazol models of epilepsy. mAterIAl And methods: Mice divided in 8 groups (n = 6) were pretreated intraperitoneally 30 min before pentylenetetrazol (50 mg/kg) or bicuculline (1 mg/kg) with saline 0.1ml/10 g body weight or lamotrigine 10 mg/kg, 15 mg/kg or 20 mg/kg, respectively. The seizure intensity and latency to the seizures 60 min after bicuculline or pentylenetetrazol injection were observed. The following scale for seizure intensity was used: 1-excitation; 2-body tremor; 3-clonic seizures of forelimbs; 4-heavy clonic seizures with rotations; 5-tonic seizures of forelimbs; 6-tonic seizures of limbs. results: The controls showed bicuculline-induced seizure intensity up to 5. lamotrigine in the higher doses used decreased the seizure intensity (p < 0.05). lamotrigine in all doses studied did not change the latency period of the first bicuculline seizure compared with the control. controls treated with pentylenetetrazol showed seizure intensity up to 4. lamotrigine in the highest dose decreased the pentylenetetrazol-induced seizure intensity (p < 0.05). lamotrigine in all studied doses increased the latency to the first pentylenetetrazol-induced seizure compared with the controls (p < 0.05). both convulsing drugs influence the brain gAbA-ergic transmitter system by competitively blocking gAbA A receptors. lamotrigine inhibits glutamate transmission and sodium channels. both neurotransmissions-glutamate and gaba are closely related in seizure control. the conclusIon is that lamotrigine has an anticonvulsive effect on both bicuculline and pentylenetetrazol seizure models, suppressing seizure intensity and influencing the latency to the first seizure.

Implications of BCRP modulation on PTZ-induced seizures in mice: Role of ko143 and metformin as adjuvants to lamotrigine

“…Seizures were induced in the current study by the gamma-aminobutyric acid (GABA)-antagonist, PTZ (Getova and Mihaylova 2011). PTZ is widely used in experimental studies to create a chemically-induced seizure model by suppressing inhibitory synapses and increasing neuronal activity.…”

“…All drugs and chemicals were given in a single dose. In groups 4,5 and 6, PTZ was given immediately after LTG (Getova and Mihaylova 2011 ).…”

“…G2:Lamotrigine-treated healthy mice (LTG): mice received LTG (20 mg/kg) i.p., G3: Acute seizures (A.S) mice (PTZ): mice received PTZ (50 mg/kg) i.p., G4: Lamotrigine-treated A.S mice (LTG + PTZ): mice received LTG (20 mg/kg) + PTZ (50 mg/kg) i.p. (Getova and Mihaylova 2011), G5: Ko143 + LTG treated A.S mice (Ko143 + LTG + PTZ): mice received Ko143 (15 mg/kg) i.p. one hour before injection of LTG + PTZ (Wanek et al 2011); Allen et al 2002), G6: Metformin + LTG treated A.S mice (MET + LTG + PTZ): mice received metformin (200 mg/kg) i.p.…”

Interleukin 6 trans-signaling regulates basal synaptic transmission and sensitivity to pentylenetetrazole-induced seizures in mice

“…No effects were observed at 25 mg/kg, while at 50 mg/kg all three animals showed and survived an epileptic event, and all animals injected with a dose ≥ 75 mg/kg died following the seizure. To assess the severity of convulsions we used a standard Racine test, consisting in the following scale: stage 0—normal behavior; stage 1—hypoactivity, immobility; stage 2—rigidity, whisker twitching; stage 3—reared, rigid posture, some automatisms (e.g., forelimb pawing, head bobbing, tail whipping); stage 4—intermittent rearing and falling with forelimb/jaw clonus, stage 5—continuous rearing and falling > 30 s or continuous jumping (popcorning); stage 6—generalized tonic‐clonic seizures with whole body convulsions (Getova & Mihaylova, ). For each 5‐minute interval the highest seizure stage reached was recorded.…”

Evaluation of Teratogenic Activity of Antiepileptic Drug Lamotrigine in Mouse Fetuses

“…Therefore, the observed fetal complications could not be attributed merely to LTG. So far, a few research studies have been conducted to explore the physiological mechanisms of LTG and its potential therapeutic applications in mice models of epilepsy 17,19 but there are limited studies on LTG teratogenicity. Additionally, most studies have considered oral intake of the drug.…”