• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.169-177
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• 2017

Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine $(5-HT)_3$ receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine ($1{\sim}300{\mu}M$) resulted in a concentration-dependent reduction in peak amplitude of currents induced by $3{\mu}m$ of 5-HT for an $IC_{50}$ value of $28.2{\pm}3.6{\mu}M$ with a Hill coefficient of $1.2{\pm}0.1$. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, $5-HT_3$-mediated currents evoked by 1 mM dopamine, a partial $5-HT_3$ receptor agonist, were inhibited by lamotrigine co-application. The $EC_{50}$ of 5-HT for $5-HT_3$ receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate $5-HT_3$ receptor desensitization, inhibited $5-HT_3$ receptor currents in a concentration-dependent manner. The deactivation of $5-HT_3$ receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of $5-HT_3$ receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the $5-HT_3$ receptor currents. These results indicate that lamotrigine inhibits $5-HT_3$-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization.

• 대한임상독성학회지
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• 제6권2호
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• pp.142-145
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• 2008

Lamotrigine is a newer anti-epileptic drug for adjunctive treatment of refractory epilepsy, partial seizures, generalized tonic-clonic seizures, and bipolar disorder. Lamotrigine overdose causes serious central nervous and cardiovascular problems, but reports are uncommon. Few lamotrigine overdoses have been described because anti-epileptic drug use is limited and usually used with combination of other anti-epileptic drugs. In addition, most patients visit emergency departments with multi-drug overdoses, so few cases of lamotrigine poisoning alone exist. We had a female patient visit our emergency department a couple of hours after a lamotrigine overdose treated with intravenous hydration and urine alkalization by NaHCO3. She recovered successfully without any evidence of renal injury. However, she developed profound rhabdomyolysis, a previously unreported complication of this medication. We suggest that serial creatine kinase levels should be measured after lamotrigine poisoning.

• Clinical and Experimental Pediatrics
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• 제57권3호
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• pp.153-156
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• 2014

Toxic epidermal necrolysis is an unpredictable and severe adverse drug reaction. In toxic epidermal necrolysis, epidermal damage appears to result from keratinocyte apoptosis. This condition is triggered by many factors, principally drugs such as antiepileptic medications, antibiotics (particularly sulfonamide), nonsteroidal anti-inflammatory drugs, allopurinol, and nevirapine. Lamotrigine has been reported potentially cause serious cutaneous reactions, and concomitant use of valproic acid with lamotrigine significantly increases this risk. We describe a case of an 11-year-old girl with tic and major depressive disorders who developed toxic epidermal necrolysis after treatment with lamotrigine, and who was diagnosed both clinically and pathologically. Children are more susceptible to lamotrigine-induced rash than adults, and risk of serious rash can be lessened by strict adherence to dosing guidelines. Unfortunately, in our case, the patient was administered a higher dose than the required regimen. Therefore, clinicians should strictly adhere to the dose regimen when using lamotrigine, especially in children.

• Clinical and Experimental Pediatrics
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• 제60권6호
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• pp.189-195
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• 2017

Purpose: The purpose of this study was to investigate the effects of lamotrigine for the treatment of attention-deficit hyperactivity disorder (ADHD) symptoms in children with epilepsy. Methods: Pediatric patients newly diagnosed with epilepsy (n=90 [61 boys and 29 girls]; mean age, $9.1{\pm}3.4years$) were enrolled. All patients were evaluated with the Korean ADHD rating scale (K-ARS)-IV before treatment with lamotrigine and after doses had been administered. The mean interval of ADHD testing was approximately 12.3 months. The initial dosage of lamotrigine was 1 mg/kg/day (maximum 25 mg/day for the first 2 weeks), and increased by 1 mg/kg every 2 weeks until titrated up to 7 mg/kg/day (or maximum 200 mg/day). Results: The mean ADHD test score of the 90 subjects was $17.0{\pm}1.8$ at baseline. It was slightly reduced to $15.6{\pm}1.7$ after lamotrigine monotherapy (P>0.01). Prior to treatment, a total of 31 patients (34.4%) met the diagnostic criteria for ADHD according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, Of these 31 patients, 27 (87.1%) had significantly improved ADHD scores with lamotrigine monotherapy ($28.0{\pm}1.6$ reduced to $18.1{\pm}2.6$, P<0.001). Among these 27 patients, 25 (92.6%) showed normalized electroencephalogram (EEG) and 26 (96.3%) achieved total freedom from seizures within 12 months of the initiation of lamotrigine monotherapy. Conclusion: The results from our study show that lamotrigine had a positive effect in pediatric epilepsy patients by reducing ADHD symptoms, preventing seizures, and normalizing EEG. However, further research is required to determine whether lamotrigine is efficacious against ADHD symptoms independent of its effects on epileptic seizures.

• The Korean Journal of Pain
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• 제18권2호
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• pp.118-123
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• 2005

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 $300{\mu}g$) was administered intrathecally. Thereafter, the dose-response curves and 50% effective dose ($ED_{50}$) 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 ($ED_{50}=61.7{\mu}g$). Mild motor weakness was observed with $300{\mu}g$ 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.

• Clinical and Experimental Pediatrics
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• 제52권3호
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• pp.389-391
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• 2009

AHS는 항경련제에 의한 부작용으로 드물게 발생하지만 생명을 위협할 수 있는 지연형 면역반응이다. 보통 항경련제 복용 후 1-8주 사이에 고열, 피부발진, 림프절병증의 임상 증세를 나타내고, 혈액, 간, 신장, 또는 폐 등의 내부 장기를 침범한다. AHS는 항경련제에 의한 부작용으로 증상이 전신적으로 다양하게 나타날 수 있다. 그리고 전염성 단핵구증이나 가와사키병과 같은 전신적 질환들과도 유사한 임상증상들을 보이기 때문에 이런 질환들과 감별하는 것이 중요하고 사망률도 10%에서 보고되고 있어 조기에 발견하고 치료하는 것이 중요하다. 저자들은 임상증상과 초기 검사가 전염성 단핵구증과 비전형적 가와사키병과 매우 유사한 lamotigine에 의한 AHS 1예를 보고하는 바이다.

• The Korean Journal of Physiology and Pharmacology
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• 제18권3호
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• pp.269-278
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• 2014

Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.

• Journal of Electrochemical Science and Technology
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• 제13권2호
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• pp.292-307
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• 2022

The study presents kinetics of degradation and mineralization of an anti-epileptic drug Lamotrigine (LAM) in the aqueous matrix by electrochemical advanced oxidation process (EAOP) on Ti/DSA (Ta₂O₅-Ir₂O₅) and Stainless Steel (SS) anodes using sodium sulphate as supporting electrolyte. On both the anodes, kinetic behaviour was pseudo-first-order for degradation as well as mineralization of LAM. On Ti/DSA anode, maximum LAM degradation of 75.42% was observed at an associated specific charge of 3.1 (Ah/litre) at a current density of 1.38 mA/cm² and 100 ppm Na₂SO₄ concentration. Maximum mineralization attained was 44.83% at an associated specific charge of 3.1 (Ah/litre) at a current density of 1.38 mA/cm² and 50 ppm concentration of Na₂SO₄ with energy consumption of 2942.71 kWh/kgTOC. Under identical conditions on SS anode, a maximum of 98.92% LAM degradation was marked after a specific charge (Q) of 3.1 (Ah/litre) at a current density of 1.38 mA/cm² and 100 ppm concentration of Na₂SO₄. Maximum LAM mineralization on SS anode was 98.53%, marked at a specific charge of 3.1 (Ah/litre) at a current density of 1.38 mA/cm² and 75 ppm concentration of Na₂SO₄, with energy consumption of 1312.17 kWh/kgTOC. Higher Mineralization Current Efficiency (MCE) values were attained for EAOP on SS anode for both degradation and mineralization due to occurrence of combined electro-oxidation and electro-coagulation process in comparison to EAOP on Ti/DSA anode due to occurrence of lone electro-oxidation process.

• 우울조울병
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• 제16권3호
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• pp.134-139
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• 2018

Objectives : Treatment for bipolar disorder is often complicated by various clinical situations. We undertook a survey of expert opinions to facilitate clinical decisions in special situations such as weight gain, metabolic syndrome, hyperprolactinemia, genetic counseling, and treatment adherence. Methods : A written survey that asked treatment strategies related to safety and tolerability, was prepared focused on weight gain, antipsychotic related hyperprolactinemia, lamotrigine related skin rash, treatment non-adherence and genetic counseling. Sixty-one experts of the review committee completed the survey. Results : In the case of weight gain related to medications, experts preferred exercise and education for diet-control. First chosen medications were lamotrigine, aripiprazole and ziprasidone. Recommendations based on expert survey results for treatment of bipolar patients in other special situations are outlined. Conclusion : With limitation of expert opinions, authors hope that results of this study provide valuable information to make clinical decisions about treatment of bipolar disorder in complicated situations.

• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.565-570
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• 2010

목 적: LTG의 국외에서의 임상 연구는 다양한 발작과 간질증후군에 단일 또는 보조요법으로서 넓은 범위의 작용을 한다고 보고되었다. 국내에서는 아직까지 소아연령에서의 LTG 초기 단일요법에 대한 연구보고가 거의 없다. 이에 저자들은 단일 병원의 전향적 자료 분석을 통한 소아 간질 환자에서의 단일 LTG 약물요법의 효용성과 안정성에 대해 연구하고자 하였다. 방 법: 2002년 9월부터 2009년 6월까지 간질약 복용 병력이 없이 간질로진단 받고 LTG을 복약하였던 소아 환자 148명을 대상으로 전향적 연구를 통해 효용성과 안정성을 연구하였다. 결 과: 대상 환아 중 초기 단일 요법으로 LTG을 복용 후 최소 6개월간 외래 추적 관찰했을 때 발작이 전혀 없었던 환아(완전 관해군)는 87명(78.4%, n=111)이었고 발작 감소를 보인 환아(부분 관해군)는 13명(11.7%), 발작이 이전과 같은 빈도이거나 오히려 악화된 경우(발작 지속군)는 11명(9.9%)이었고 부작용인 피부발진과 틱 장애로 LTG복약을 중지해야만 했던 환아가 8명이었다. 발작의 유형에 따른 치료 결과는 완전 관해군을 기준으로 할 때 부분 간질에서 전신간질보다 발작 완해률이 81.6% vs 44.8 %로 더 높았다(${\kappa}^2$=26.75, $P$<0.05). 발작 유형별로는 각각 CPS가 41명(75.9%, n=54), BRE가 30명(90.9%, n=33) absence seizure가 3명(30.0%, n=10) JME가 5명(35.7%, n=14), IGE가 5명(100.0%, n=5)으로 완전 관해 되었고 IGE와 BRE에서 완전 관해률이 각각 100.0%, 90.9%로 높았다. 투약 기간 중 부작용이 관찰된 환아는 모두 17명(14.3%, n=119)이었다. 피부 발진이 11명, 틱 장애가 3명, 간염이 1명, 결막염이 1명, 졸림이 1명에서 관찰되었고 피부 발진이 생긴 환아 11명 중 7명은 발진이 심하여, 1명은 틱 증상이 심하여 투약을 중지하였다. Stevens-Johonson 증후군 같은 심각한 부작용이 생겼던 환아는 없었다. 결 론: 본 연구 결과 LTG 초기 단일요법의 효용성은 국외 보고와 비교하여 우수하거나 큰 차이가 없었으며, 위중한 부작용 사례는 없었다. 소아 간질 환자, 특히 양성 로란딕 간질 환자와 특발성 전신발작 환자에서 LTG의 초기 단일 요법 치료에 매우 우수한 것으로 사료되어 문헌 고찰과 함께 보고하는 바이다.