Lamotrigine In Rats Research Articles

Safety evidence on the administration of Fucus vesiculosus L. (bladderwrack) extract and lamotrigine: data from pharmacokinetic studies in the rat

Fucus vesiculosus is often incorporated in weight loss dietary supplements to improve weight loss in overweight adults. Obesity is a common condition in epilepsy patients and is indeed increasing in refractory epilepsy and in patients under polytherapy. Since lamotrigine (LTG) is a first-line antiepileptic drug, used in monotherapy or adjunctive therapy, the main objective of this work was to investigate the potential pharmacokinetic-based interactions between F. vesiculosus and LTG in rats. In a first pharmacokinetic study, a single oral dose of F. vesiculosus extract (575 mg/kg, p.o.) was co-administered with a single-dose of LTG (10 mg/kg, p.o.). In a second study, rats were orally pretreated with F. vesiculosus extract (575 mg/kg/day, p.o.) for 14 days and received LTG (10 mg/kg, p.o.) on the 15th day. In the control groups, rats received water instead of the extract. After LTG administration, blood samples were taken until 96 h post-dose, and LTG concentrations measured in plasma were submitted to a non-compartmental pharmacokinetic analysis. The co-administration of F. vesiculosus extract and LTG caused no significant changes in the drug kinetics. However, the repeated pretreatment with F. vesiculosus extract significantly reduced the peak concentrations of LTG and caused a slightly decrease in the extent of systemic drug exposure. Overall, based on these results, no significant clinical impact is expected from the administration of F. vesiculosus dietary supplements and LTG.

Evaluation of the effects of Citrus aurantium (bitter orange) extract on lamotrigine pharmacokinetics: Insights from in vivo studies in rats

Citrus aurantium extracts have thermogenic and lipolytic activities and are largely used for weight loss/management. Once epilepsy and obesity are prevalent comorbid conditions and herb-drug interactions can compromise antiepileptic drugs safety, we aimed to evaluate the effects of C. aurantium extract on the pharmacokinetics of lamotrigine (LTG) in rats. In the first pharmacokinetic study, a single oral dose of C. aurantium extract (164 mg/kg; p.o.) was administered with a single oral dose of LTG (10 mg/kg; p.o.). In the following study, the C. aurantium extract was daily administered (164 mg/kg; p.o.) during 14 days followed by a single dose of LTG (10 mg/kg; p.o.) on the 15th day. From the pharmacokinetic analysis, no significant effects were observed after the co-administration of C. aurantium extract and LTG. After the 14-day pre-treatment period, the main effects of the extract were limited to a significantly decrease in the time to reach peak drug concentration (tmax;p < 0.05). Considering the minor effects induced by C. aurantium extract on the pharmacokinetics of LTG in rats, no relevant interactions are expected to occur in the clinical practice. Notwithstanding, C. aurantium safety in patients under LTG therapy should be further assessed in controlled clinical trials.

Effects of Paullinia cupana extract on lamotrigine pharmacokinetics in rats: A herb-drug interaction on the gastrointestinal tract with potential clinical impact

Paullinia cupana-containing preparations are being consumed worldwide for weight reduction. As obesity and epilepsy are common comorbidities and lamotrigine (LTG) is a broad-spectrum antiepileptic drug, it is likely to find epilepsy patients taking P. cupana and LTG simultaneously. Thus, this work aimed to investigate the potential interaction between P. cupana extract and LTG in rats. In a study, rats were orally co-administered with a single-dose of P. cupana extract (821 mg/kg) and LTG (10 mg/kg). In another study, rats were orally pre-treated for 14 days with P. cupana extract (821 mg/kg/day) receiving LTG (10 mg/kg, p.o.) on the 15th day. Rats of the respective control groups received the corresponding volume of the extract vehicle. LTG concentrations were determined at several post-dose time-points and submitted to a non-compartmental pharmacokinetic analysis. The co-administration of P. cupana and LTG induced a significant reduction of LTG Cmax and AUC0-24 and prolonged the mean residence time. However, no significant effects were observed on LTG pharmacokinetics following a 14-day pre-treatment period with the extract. In this study changes in the body weight of rats and in some biochemical parameters were also evaluated. Overall, the results revealed a pharmacokinetic-based herb-drug interaction between P. cupana extract and LTG, mainly after their co-administration.

Effect of lamotrigine, levetiracetam & topiramate on neurobehavioural parameters & oxidative stress in comparison with valproate in rats.

Background & objectives:Though newer antiepileptic drugs are considered safer than conventional antiepileptics, the effects of lamotrigine, levetiracetam and topiramate on neurobehavioural functions are yet to be established. This study evaluated neurobehavioural parameters and oxidative stress markers in brain tissue of rats treated with lamotrigine, levetiracetam and topiramate compared to sodium valproate.Methods:Five groups of male Wistar rats were treated respectively with normal saline (control), sodium valproate (370 mg/kg), lamotrigine (50 mg/kg), levetiracetam (310 mg/kg) and topiramate (100 mg/kg) for 45 days. Neurobehavioural parameters were assessed using elevated plus maze (EPM), actophotometer, rotarod, passive avoidance and Morris water maze (MWM) at baseline and at the end of treatment. Oxidative stress parameters [malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD)] were estimated in rat brain at the end of treatment.Results:Valproate and lamotrigine showed no significant effect on learning and memory in passive avoidance and MWM tests. However, levetiracetam and topiramate reduced retention memory significantly as compared to control (P<0.01) and lamotrigine (P<0.05) groups. Performances on EPM, rotarod and actophotometer were not significantly different between the groups. In comparison to control group, MDA was higher in the levetiracetam and topiramate (360.9 and 345.9 nmol/g of homogenized brain tissue, respectively) groups. GSH and SOD activity were significantly reduced by valproate and levetiracetam treatment. Lamotrigine did not induce significant oxidative stress.Interpretation & conclusions:Long-term and therapeutic dose treatment with levetiracetam and topiramate significantly impaired learning and memory, which was not seen with valproate and lamotrigine in rats. Levetiracetam, topiramate and valproate augmented oxidative stress, whereas lamotrigine has little effect on it. These antiepileptic drugs are used in clinical practice, hence pharmacovigilance studies are required to evaluate their safety profile.

ANALGESIC EVALUATION OF NOVEL ANTICONVULSANT WITH A CONVENTIONAL ANALGESIC IN DUAL PAIN MODEL OF RAT

G abapentin and carbamazepine like anti epileptics a re being used now a days to treat a number of disease s associated with neuropathic pain. The aim of this stu dy is to observe whether novel anticonvulsants are able to pro duce analgesic response in pain conditions of acute and chronic type . This study observed the analgesic effect of lamo trigine in rats by bi phasic noci ceptive pain model of formalin test and compared its potency with a convention al opioid analgesic tramadol. Per oral adminis tration of l amotrigine produced no s i gnificant effect on early phase response of formalin test but significantly suppress ed the late phase response. We conclude that lamotrigine has antinociceptive effect in chronic inflammatory pain as seen by its effect on late phase of f ormalin test while

Antidepressant, anticonvulsant and side effect profile of lamotrigine in rats

Antidepressant, anticonvulsant and side effect profile of lamotrigine in rats

The Mechanical Antiallodynic Effect of Intrathecal Lamotrigine in Rats with Spinal Nerve Ligation

Background: A nerve ligation injury may produce a tactile allodynia. The effects of intrathecally delivered lamotrigine on allodynia induced due to fifth and sixth lumbar spinal nerves ligation in rats, using lumbar intrathecal catheters were examined. Methods: Sprague-Dawley rats (body weight 160-180 g) were prepared by tightly ligating the fifth and sixth left lumbar spinal nerves, with the implantation of a chronic intrathecal catheter for drug administration. Mechanical allodynia and allodynic threshold were measured using von Frey filaments and the updown method, respectively. After the baseline hind paw withdrawal thresholds had been obtained, lamotrigine (10, 30, 100 and 300) was administered intrathecally. Thereafter, the dose-response curves and 50% effective dose () were obtained. Motor dysfunction was assessed by observing the righting/stepping reflex responses and abnormal weight bearing. Results: Intrathecal administration of lamotrigine produced a dose-dependent antiallodynic action ( = 61.7). Mild motor weakness was observed with 300 lamotrigine, but no severe motor impairment was found. Conclusions: It is suggested that intrathecal lamotrigine could produce moderate antagonism of mechanical allodynia at the spinal level in a rat neuropathic pain model with minimal motor weakness.

Relationship between plasma and brain levels and the anticonvulsant effect of lamotrigine in rats

The aims of the present research were to characterize the plasma and brain concentration–time profiles of lamotrigine after its acute administration and to establish the relationship between these profiles and the anticonvulsant effect of lamotrigine in rats. Adult male Wistar rats were given 10 mg/kg of lamotrigine intraperitoneally. The lamotrigine profiles in plasma and brain were determined at predetermined times over 120-h post-dose. The anticonvulsant profile against maximal electroshock seizure stimulation was determined over 48 h after dosing. After injection, lamotrigine rapidly appeared in both plasma and brain, suggesting ready penetration of the blood–brain barrier. A linear relationship was established between lamotrigine plasma and brain levels. A linear relationship was also defined between lamotrigine brain levels and the anticonvulsant response. The correspondent plasma levels were also well correlated with the anticonvulsant effect from the moment that the plasma–brain system had reached equilibrium.

The effect of parenteral imipramine on the oral absorption of lamotrigine in rats

The interaction between imipramine and lamotrigine was investigated following the acute administration of lamotrigine (20 mg kg−1, p.o.) alone or together with imipramine (25 mg kg−1, i.p.) to rats. Similarly, the same doses of lamotrigine alone or when they were given together with imipramine (15 mg kg−1, i.p.) were administered to rats chronically for 5 days. Plasma samples were collected at 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0 and 24.0 h after lamotrigine administration. An assay of lamotrigine in plasma was performed using a high-performance liquid chromatographic (HPLC) method. The concomitant administration of imipramine (25 mg kg−1, i.p) with lamotrigine (20 mg kg−1, p.o.) acutely, resulted in a significant (P<0.05) decrease in the maximum plasma concentration (Cmax), the mean area under the plasma concentration–time curve (AUC) and the half-life (t1/2), and a significant decrease (P<0.001) in the time to reach maximum concentration (tmax), as compared to those obtained for lamotrigine alone. Similarly, the chronic administration of imipramine together with lamotrigine lead to significant decreases in Cmax, AUC and t1/2 while the tmax remained unchanged. These results suggest that a significant decrease in the absorption of lamotrigine occurs when it is given acutely or chronically together with the antidepressant imipramine.