Congenital myotonia is a hereditary disorder of the skeletal muscle. The most characteristic features of the disease are myotonia and variable muscular hypertrophy. Molecular biologic investigations have revealed that mutations in the gene of the human skeletal muscle chloride ion channel protein are a cause of the disease. The Becker's type congenial myotonia is clinically similar to the autosomal dominantly inherited congenital myotonia (Thomsen's disease). Both disorders are characterized electrophysiologically by increased excitability of muscle fibers, reflected in clinical myotonia. In general, Becker's type congenital myotonia is more severe than Thomsen's disease in muscular hypertrophy and weakness. The authors recently experienced a 25-year-old female patient who has no family-related disease history and who has conspicuous muscular hypertrophy and the stiffness with muscles which occurred from the age of 3 or 4. Clinically she showed the authors a percussion myotonia. On electrophysiological study, exercise and repetitive stimulation of the abductor digiti quinti muscle disclosed a decline in the compound muscle action potential. Biopsy of biceps muscle revealed enlargement of muscle fibers with marked nuclear internalization. After the oral taking the Mexiletine, the patient showed a favorable turn a little with her stiffness of muscles. So we authors are reporting one case of Becker's type congenital myotonia with review of literatures.
Action Potentials ; Adult ; Biopsy ; Chloride Channels ; Female ; Humans ; Hypertrophy ; Mexiletine ; Muscle, Skeletal ; Muscles ; Myotonia ; Myotonia Congenita*

The effect of oral mexiletin was evaluated by a 10-day double-blind cross-over protocol on 10 subjects with chronic stable high-frequency ventricular premature beats referred to our cardiology clinic from February through July, 1982. Total daily doses were either 450mg or 600mg in three divided portions depending on body weight. The frequency of the premature ventricular beats was measured by 3 separate 24-hour ambulatory EKG recordings by dual-channel Holter monitor on each patient. Mexiletine was judged to be effective in suppressing the ventricular arrhythmias when the 24-hour PVC-counts during the study-drug period showed a decrease by 80% and the hourly average PVC-counts by 70% compared with those of the equivalent intervals of both the baseline and the placebo periods. Mexiletine was effective in 5 of the 10 subjects. Mild tremor and anorexia were noted in 2 patients, but they were able to comply with the study protocol in spite of these minor side effects. Blood level measurements were not done in this study for lack of such facility, the utilization of which would undoubtedly enhance the therapeutic effectiveness of the antiarrhythmic agent in the individualization of treatment.
Anorexia ; Arrhythmias, Cardiac ; Body Weight ; Cardiac Complexes, Premature* ; Cardiology ; Electrocardiography ; Humans ; Mexiletine* ; Tremor ; Ventricular Premature Complexes

AIMTo establish an HPLC-fluorescent spectrometric method for the determination of mexiletine hydrochloride in plasma after derivatization with fluram.

METHODSFluram acetone solution was added to the deproteinized plasma with acetone to obtain the derivative of mexiletine. The HPLC method was performed on a column of Allitima C18 (150 mm x 4.6 mm, 5 microns) with the mobile phase of methanol-water-diethylamine-phosphoric acid buffer (2.4 mol.L-1, pH 4.0) (70:28:2), and the detective wavelength were set at Ex 392 nm and Em 480 nm.

RESULTSMexiletine has a liner range over the concentration range from 0.100-6.400 mg.L-1. The lowest detectable concentration of this method was 5 micrograms.L-1 (S/N > or = 4). The intra-day and inter-day RSDs were 1.34%-5.31%, respectively.

CONCLUSIONThis method is simple, selective and can be used for therapeutic drug monitoring (TDM) and pharmacokinetic studies of mexiletine.

Anti-Arrhythmia Agents ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Fluorescamine ; chemistry ; Humans ; Mexiletine ; blood ; pharmacokinetics

The antiarrhythmic effect of Mexiletine was evaluated in five patients with recurrent ventricular tachycardia and in twelve patients with frequent premature ventricular contractions. Electrophysiologic study was performed on the the patients with recurrent ventricular tachycardia before and after the administration of Mexiletin(600-800mg/day). The antiarrhythmic effects of Mexiletine in the patients with frequent premature ventricular contraction was assessed by ambulatory electrocardiography. The results were as follows: 1) In all of the five patients with recurrent ventricular tachycardia, sustained ventricular tachycardia was induced by programmed ventricular stimulation. However, on repeated electrophysiologic study performed while receiving Mexiletine, ventricular tachycardia was not induced in four patients and non-sustained ventricular tachycardia was induced in one patients. 2) The number of premature ventricular contraction was decreased markedly in seven patients(58.3%) with frequent premature ventricular contractions. 3) Minimal side effects, mild indigestion and tremor, were recorded in 3 cases(23%) while receiving Mexiletine 600 mg/day. The higher dose was associated with more frequent and severe side effects.
Dyspepsia ; Electrocardiography, Ambulatory ; Humans ; Mexiletine* ; Tachycardia, Ventricular ; Tremor ; Ventricular Premature Complexes

The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved the motor performance. However, administration of indomethacin (100 mg/kg, i.p.) attenuated the neuroprotective effect of carbamazepine. Mexiletine (50 mg/kg, i.p.) did not produce significant neuroprotective effect. It may be concluded that the neuroprotective effect of carbamazepine may be due to increase in synthesis of neurosteroids perhaps by activating enzyme (3alpha HSD) as indomethacin attenuated the neuroprotective effect of carbamazepine. The sodium channel blocking effect of carbamazepine may not be involved in neuroprotection as mexiletine, a sodium channel blocker, did not produce significant neuroprotective effect.
Animals ; Carbamazepine ; Carotid Arteries ; Hand Strength ; Indomethacin ; Mexiletine ; Mice* ; Neuroprotective Agents ; Neurotransmitter Agents ; Reperfusion ; Sodium Channels

Long QT syndrome is a cardiac disorder of repolarization which is characterized by elctrocardiographic abnormalities including prolonged QT interval, T-wave abnormalities and polymorphic ventricular tachycardia known as Torsades de Pointes. Its clinical manifestation are recurrent syncope, seizure, and sudden death. Recently,we experienced Torsades de Pointes(TdP) by head-up tilt test in 24 year-old female patient presenting recurrent syncope and long QT interval. Beta-blocker and left cervicothoracic sympathetic ganglionectomy were not effictive, then we tried mexiletine. After mexiletine medication, the QT interval was significantly shortened and there was no more syncope.
Death, Sudden ; Female ; Ganglionectomy ; Humans ; Long QT Syndrome* ; Mexiletine ; Seizures ; Syncope ; Tachycardia, Ventricular ; Torsades de Pointes* ; Young Adult

Erythromelalgia is a rare disease characterized by palmar and plantar erythema, burning pain and local increase in temperature. Secondary erythromelalgia most commonly appears secondary to myeloproliferative disorders, essential thrombocytosis and polycythemia vera. The pain associated with erythromelalgia is often severe and recalcitrant. So far no properly performed therapeutic trials have been published. We present a case of erythromelalgia of both hands and feet in a 52 year old man. A twice daily cervical and lumbar epidural block of mepivacaine 0.5% and mexiletine 100 mg given orally resuletd in complete resolution of the syndrome. After 3 months, the symptom recurred mildly.
Bupivacaine* ; Burns ; Erythema ; Erythromelalgia* ; Foot ; Hand ; Humans ; Mepivacaine ; Mexiletine* ; Middle Aged ; Myeloproliferative Disorders ; Polycythemia Vera ; Rare Diseases ; Thrombocytosis

The antiarrhythmic effect of oral Mexiletine was evaluated by Holter monitoring on 10 subjects with chronic high-frequency ventricular premature complexes and ventricular tachycardia referred to our cardiology clinic of Severance Hospital from June, 1982 through September, 1983. The frequency of the ventricular premature complexes and the ventricular tachycardia was measured by 24-hour ambulatory electrocardiography on each patient before and during the administration of Mexiletine(450-600 mg/day). The results were as follows : 1) In 10 patients with ventricular tachycardia total suppression of ventricular tachycardial was demonstrated in 8 patients during the administration of oral Mexilletine. 2) The number of the ventricular premature complexes was reduced markedly in 6 out of the 10 patients. 3) Side effects occurred in 5 out of 10 patients. These include tremor, weakness, dry mouth, indigestion, anorexia, chest discomfort, and dizziness but were tolerated except in one.
Anorexia ; Arrhythmias, Cardiac* ; Cardiology ; Dizziness ; Dyspepsia ; Electrocardiography, Ambulatory* ; Humans ; Mexiletine* ; Mouth ; Tachycardia, Ventricular ; Thorax ; Tremor ; Ventricular Premature Complexes

BACKGROUND AND OBJECTIVES: Congenital long QT syndrome (LQTS) is characterized by the prolongation of the QT interval, frequent episodes of syncope and Torsades de Pointes (TdP). The clinical features and electrocardiographic findings in Korean patients with LQTS have not been reported. SUBJECTS AND METHODS: We retrospectively analyzed the clinical characteristics, ECG features and response to treatments in 11 patients (6 men, 5 women) with congenital LQTS. RESULTS: The mean age at the time of the first episode was 19.4+/-22.6 years old (range: 170 years). Clinical presentations were syncope, seizure or sudden cardiac death (SCD). Predisposing factors included exercise, sudden startle or sleep. Only three patients showed familial histories of syncope or SCD. The average QTc interval was 0.58+/-0.05 second (range: 0.47-0.61 seconds). T wave morphologies were classified as normal-appearing, broad-based, low amplitude/bifid or late onset. For its management, bblockers were used in 7 patients. In 2 patients, whose clinical events were related with to an increased vagal tone or were aggravated by bblocker therapy, mexiletine was prescribed. When bradycardia or AV block was documented, pacemakers were implanted. For 2 patients at high risk of sudden cardiac death, cardioverter-defibrillators were implanted. During a mean follow up period of 23.5+/-20.2 months (range: 364 months), symptoms (cardiac arrest) recurred in 1 patient. CONCLUSION: Congenital LQTS is a heterogeneous disease, showing diverse clinical manifestations, ECG features, and response to pharmacological management. Further research on the genotype-phenotype relationship will refine the management, enabling gene-specific treatment of this life-threatening disease.
Arrhythmias, Cardiac ; Atrioventricular Block ; Bradycardia ; Causality ; Death, Sudden ; Death, Sudden, Cardiac ; Electrocardiography* ; Follow-Up Studies ; Humans ; Long QT Syndrome* ; Male ; Mexiletine ; Retrospective Studies ; Seizures ; Syncope ; Torsades de Pointes

Chronic pain is a multifactorial condition with both physical and psychological symptoms, and it affects around 20% of the population in the developed world. In spite of outstanding advances in pain management over the past decades, chronic pain remains a significant problem. This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel alpha2-delta ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment.
Analgesics, Opioid ; Antidepressive Agents ; Calcium Channels ; Capsaicin ; Chronic Pain ; Fibromyalgia ; Lidocaine ; Ligands ; Mexiletine ; N-Methylaspartate ; Neuralgia ; Neuromuscular Agents ; Norepinephrine ; Pain Management ; Serotonin ; Sleep Deprivation ; Tramadol