Determination of mexiletine hydrochloride by rose Bengal probe using dual-wavelength resonance light scattering technology / 药学学报

The resonance light scattering (RLS) spectral characteristics of the interaction between rose Bengal and mexiletine hydrochloride in the presence of cetylpyridinium bromide were investigated. A dual-wavelength resonance light scattering (DWO-RLS) method for the determination of mexiletine hydrochloride in drugs was established. In a weakly acidic solution, rose Bengal interacts with mexiletine hydrochloride and cetylpyridinium bromide to form a red ternary ion association complex, which led to a significantly enhanced resonance light scattering signal and produced two strong characteristic scattering peaks at 372 nm and 596 nm. In these two wavelengths the mass concentration of mexiletine hydrochloride was in the range of 0.004 to 0.65 mg·L-1 and had a good linear relationship with the resonance light scattering enhancement intensity (ΔIRLS), with detection limits of 0.003 2 mg·L-1 (372 nm) and 0.003 8 mg·L-1 (596 nm), respectively. When measured by the dual-wavelength resonance light scattering (DWO-RLS) technique, the detection limit was lower, only 0.001 8 mg·L-1. When the DWO-RLS method was applied to the determination of mexiletine hydrochloride in commercially available mexiletine hydrochloride tablets, and the recovery was 98.5%-103%, and the relative standard deviation was 2.0%-2.7%.

Dose-dependent analgesic activity of mexiletine on thermally induced pain in rats

Background: Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. In spite of many advances in pain research, we are unable to deal in an effective way. The cost for new drug development is increasing day by day. Drug repurposing is an approach to look for new use in drugs that are already approved for other indications. Mexiletine is a sodium channel blockers that is being approved for treatment of arrhythmias. It is being tried in treatment of various painful conditions. The present study is to evaluate the dose-dependent analgesic activity of mexiletine with ibuprofen.Methods: The analgesic activity of mexiletine was compared at doses of 15mg/kg, 30mg/kg and 45mg/kg with the standard dose of ibuprofen at 10mg/kg in male Wistar rats in thermal model of tail flick analgesiometer.Results: At lower doses (15mg/kg) of mexiletine, analgesic activity of ibuprofen was significantly higher. At higher doses (30 mg/kg and 45 mg/kg) of mexiletine, it was observed that there is no significant difference between the analgesic activities of both drugs.Conclusions: Mexiletine demonstrated a dose-dependent analgesic activity. There was no statistically significant difference between the analgesic activities of higher doses of mexiletine when compared to ibuprofen.

Determination of mexiletine hydrochloride in drugs by eosin Y Rayleigh light scattering / 国际药学研究杂志

Objective: To establish a simple,rapid and novel Rayleigh light scattering(RLS)method for rapid determination of mexiletine hydrochloride in drugs. Methods: In the presence of acid Tris-HCl medium and cetylpyri- dinium bromide,eosin Y reacted with mexiletine hydrochloride to form a ternary ion association complex with two charac- teristic scattering peaks by electrostatic attraction. The detection wavelengths were 368 and 586 nm. There was a linear relationship between the mexiletine hydrochloride concentration in a certain range and the Rayleigh light scattering en- hancement intensity(ΔIRLS)of the association complex. Single-wavelength Rayleigh scattering(SWO-RLS)method or dualwavelength Rayleigh light scattering(DWO-RLS)method was used to determine the content of mexiletine hydrochloride, and the mexiletine hydrochloride content was calculated according to the regression equation of standard curve. Results: The linear ranges of mexiletine hydrochloride were 0.005-0.65 mg/L(SWO-RLS method,368 nm),0.004-0.65 mg/L (SWO-RLS method,586 nm)and 0.004-0.65 mg/L(DWO-RLS method,368 nm+586 nm),respectisely. Detection lim- its were 0.0033(SWO-RLS method,368 nm),0.0040(SWO-RLS method,586 nm)and 0.0018 mg/L(DWO-RLS method, 368 nm+586 nm),respectisely. The recovery and relative standard deviation(RSD,n=5)for a SWO-RLS method were 98.6-103% and 1.4-1.8%,respectively(SWO-RLS method,368 nm). Conclusion: The method is simple,rapid, highly sensitive and high selectie.

Effect of Neurosteroid Modulation on Global Ischaemia-Reperfusion-Induced Cerebral Injury in Mice

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.

A Case of Long QT Syndrome Type 3 Aggravated by Beta-Blockers and Alleviated by Mexiletine: The Role of Epinephrine Provocation Test

Long QT syndrome (LQTs) is an uncommon genetic disease causing sudden cardiac death with Torsade de Pointes (TdP). The first line drug treatment has been known to be beta-blocker. We encountered a 15-year-old female student with LQTs who had prolonged QTc and multiple episodes of syncope or agonal respiration during sleep. Although her T wave morphology in surface electrocardiography resembled LQTs type 1, her clinical presentation was unusual. During the epinephrine test, TdP was aggravated during beta-blocker medication, but alleviated by sodium channel blocker (mexiletine). Therefore, she underwent implantable cardioverter defibrillator implantation.

A Case of Mexiletine-induced Hypersensitivity Syndrome Presenting as Eosinophilic Pneumonia

An 82-yr-old man was presented with fever and cough accompanied by generalized erythematous rash. He had taken mexiletine for 5 months, as he had been diagnosed with dilated cardiomyopathy and ventricular arrhythmia. Laboratory studies showed peripheral blood eosinophilia and elevated liver transaminase levels. Chest radiographs showed multiple nodular consolidations in both lungs. Biopsies of the lung and skin lesions revealed eosinophilic infiltration. After a thorough review of his medication history, mexiletine was suspected as the etiologic agent. After discontinuing the mexiletine and starting oral prednisolone, the patient improved, and the skin and lung lesions disappeared. Subsequently, mexiletine was confirmed as the causative agent based on a positive patch test. Drug-induced hypersensitivity syndrome is a severe adverse reaction to drugs and results from treatment with anticonvulsants, allopurinol, sulfonamides, and many other drugs. Several cases of mexiletine-induced hypersensitivity syndrome have been reported in older Japanese males with manifestation of fever, rash, peripheral blood eosinophilia, liver dysfunction without other organ involvement. Here, we report a case of mexiletine-induced hypersensitivity syndrome which presented as eosinophilic pneumonia in a Korean male.

Epidural Block of Bupivacaine and Mexiletine for Erythromelalgia / 대한마취과학회지

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.

Efficacy of Yixinshu Capsule in treatment of premature beats / 中成药

AIM:To find a new way of treating premature beats(PB) to evaluate the efficacy and safety of Yi-(xinshu) Capsule(Radix et Rhizoma Ginseng,Radix et Rhizoma Salviae miltiorrhizae,Radix Ophiopogonis,Radix Astragali,etc.) METHODS:Randomized,controlled clinical study were conducted in 60 patients with atrial premature beats(APB),and 60 patients with premature ventricular beats(PVB).APB patients were randomly divided into two groups:Yixinshu Capsule plus Isoptin(study group,n=30) and Isoptin group(control group,n=30).PVB patients:Yixinshu Capsule plus Mexiletine(study group,n=30) and Mexiletine group(control group,n=30).Those patients were treated for four weeks.We used 24 h Holter to monitor the times of PB and myocardial ischemia in before and after treatment.RESULTS:In the study group and control group,the times of APB and PVB were decreased obviously after 4 weeks treatment(P

THE EFFECT OF THE COMBINATION OF MEXILETINE AND PROPRANOLOL ON VENTRICLE EXTRASYSTOLE / 中国药理学通报

A combination of Mexiletine and propranolol was administered in 40'patients suffering from ventricle extrasystole. The results suggest that the effect of the combination is superior to that of mexiletine administered alone