Background: There are few treatment options for patients with secondary progressive and worsening relapsing-remitting multiple sclerosis. MITOXANTRONE is an antineoplastic drug, recently approved for treatment of multiple sclerosis. MITOXANTRONE is, however, associated with doserelated cardiotoxicity, which limits its use. Objective: To investigate the possible cardiotoxicity of MITOXANTRONE in multiple sclerosis. Methods: We studied 96 patients with worsening relapsing-remitting or secondary progressive multiple sclerosis, to evaluate cardiotoxicity within one year of MITOXANTRONE therapy. This study was performed in the Multiple Sclerosis Clinic of Isfahan University of Medical Sciences from October 2003 through October 2004. Analysis of MITOXANTRONE therapy (12 mg/m2), in terms of cardiac toxicity, was conducted on patients who received at least 4 doses. Cardiac assessment was carried out every 6 months with electrocardiogram, as well as a spectral and color-flow Doppler echocardiographic examination at the time of enrollment and 6 and 12 months later. Results: Ninety-six patients were assessed over 12 months. There was no evidence of clinically-significant cardiac dysfunction. Three patients had a left ventricular ejection fraction of <10% of the base-line value and three had <50%. Conclusion: MITOXANTRONE (12 mg/m2) is effective and generally well tolerated by patients with worsening relapsing-remitting and secondary progressive multiple sclerosis. Our findings suggest that the risk for developing cardiotoxicity is low in patients with multiple sclerosis within one year of the treatment with MITOXANTRONE.

Patients with worsening relapsing remitting MS, secondary progressive MS, and progressive relapsing MS are potential candidates for treatment with MITOXANTRONE. Early identification of these patients is essential because there is emerging evidence that early and aggressive treatment might delay or limit long-term disability. Treatment with MITOXANTRONE is associated with certain adverse events, such as carditoxicity. However, the possible benefit of treatment outweighs the risks for patients with aggressive or worsening disease. With the selection of appropriate patients and careful monitoring for adverse events, MITOXANTRONE can be safely administered.

Context: MITOXANTRONE (MTX) is an antracyclin drug that is used for treatment of patients with chronic refractory multiple sclerosis (MS). Congestive heart failure (CHF) is a rare complication of this drug that may occur early, during therapy, or late, months or years after termination of therapy. Aims: The aim of this study is to evaluate the long‑ term adverse effect of MTX on cardiac function. Methods: The study involved 49 MS patients on MTX therapy because of their disease was refractory to other treatments (18 men and 31 women). They were treated in two canters related to Esfahan University of Medical Sciences. The mean age was 34. 65 ± 9. 56 years. Systolic and diastolic left ventricular (LV) functions were measured by echocardiography. The baseline echocardiographic data were collected from patients’ file. Echocardiography was repeated by a single cardiologist in 2016. Results: After MTX therapy, one patient’ s ejection fraction (EF) reduced below 50% (2%). In spite of their normal diastolic function before therapy, two patients developed diastolic dysfunction (4%). Nonparametric binominal analysis reveals that MTX therapy increased the probability of developing systolic dysfunction, early or late P < 001. Conclusions: MS patients treated with MTX are at increased risk of developing early and late‑ LV dysfunction, so all patients on MTX therapy must be periodically evaluated for these late complications.

The combination of liquid chromatography coupled to mass spectrometry (LC–MS) and acute toxicity studies with Daphnia magna was used to elucidate the water stability of the cytostatic compounds, MITOXANTRONE and chlorambucil, and their transformation products (TPs). Both compounds were rapidly degraded in water with the subsequent formation of bioactive TPs. MITOXANTRONE suffered a rapid change in its conformation with the formation of four toxic TPs, which were unaltered and stable in water along the 2-day studied period. LC-MS analyses were allowed to identify the conformational changes of MITOXANTRONE that included the loss of the two amino alcohols (N-ethylethanolamina) [C4H10NO]+, the loss of N-ethylethanolamina [C4H10NO]+ and N-methylethanolamina [C3H8NO]+, the loss of CH2OH from the original molecule and the formation of MITOXANTRONE dicarboxilic acid. Chlorambucil was also rapidly degraded in water loosing a hydroxyl group and forming a bioactive TP that further degraded within the following 12 h. The degradation of chlorambucil was also related to an exponential loss of toxic activity towards D. magna survival. The present results indicate that LC–MS methods should target TPs since field concentrations of these compounds measured in water may not reflect their toxicity.

Background: Multiple sclerosis is a leading cause of disability in young adults. MITOXANTRONE has recently been shown to be effective in ameliorating multiple sclerosis activity and reducing the relapse rate. This study aimed to assess the efficacy of MITOXANTRONE on disease activity and decreasing relapse rate in patients with multiple sclerosis in Iran.Methods: This was a clinical trial on patients who received intravenous MITOXANTRONE, 12 mg/m2 every 3 months. The study was performed at Isfahan Multiple Sclerosis Clinics, affiliated to Isfahan University of Medical Sciences. This clinical trial was conducted from October 2003 through April 2005.One hundred and forty-seven patients with worsening relapsing-remitting and secondary progressive multiple sclerosis received MITOXANTRONE, 12 mg/m2 every 3 months. Clinical assessment was made every 3 months for one year.Results: Of the 147 patients, 129 (93 females and 36 males) could successfully complete the course of our study. A significant therapeutic effect (P<0.0001) was detected for the attack rate before and after treatment. The mean attack rate 12 months before treatment was 1.10 (SD=0.95), which reduced to 0.09 (SD=0.29) during treatment.THE Mean expanded disability status scale at the beginning of the treatment was 4.32, which declined to 3.62 (P<0.0001) after one year.Conclusion: MITOXANTRONE was generally well tolerated and reduced progression of disability and clinical exacerbation in our patients. Physicians must be careful about the complications of MITOXANTRONE especially cardiotoxicity.

Objective (s): First principles calculations were performed to study four multiple sclerosis drugs namely, Ampyra, Fingolimod, MITOXANTRONE and Eliprodil in gas and liquid phases using Density Functional Theory (DFT). Computational chemistry simulations were carried out to compare calculated quantum chemical parameters for Ampyra, Fingolimod, MITOXANTRONE and Eliprodil.Materials and Methods: All calculations were performed using DMol3 code which is based on DFT. The Double Numerical basis set with Polarization functions (DNP) was used.Results: MITOXANTRONE has highest HOMO energy, global softness, solvation energy and molecular mass and lowest LUMO energy, energy gap, global hardness and total energy in comparison to Ampyra, Fingolimod and Eliprodil in gas and solvent phases. Calculations were carried out to study the interaction of covalently binding MITOXANTRONE to functionalized carbon nanotube. The MITOXANTRONE local reactivity was studied through the Fukui indices in order to predict both the reactive centers and the possible sites of nucleophilic and electrophilic attacks. The MITOXANTRONE binding energy is calculated to be 6.507 eV in gas phase and -9.943 eV in solvent phase that is a decrease in BE as the drug phase changes from gas to liquid.Conclusion: The simulation results show MITOXANTRONE is quite a reactive drug. The quantum chemical parameters of pristine nanotube and f-SWNT-MITOXANTRONE showed that reactivity of f-SWNT-MITOXANTRONE increased in comparison to pristine nanotube in both phases.

Introduction: MITOXANTRONE (MX) has been introduced as a photosensitizer drug. However, due to some side effects, the widespread use of this drug has been confronted with some limitations. Hollow gold nanoshells (HGN) have attracted considerable attention due to their interesting photochemical features that can use as nanocarrier. In this paper, the thermal response of MX and the use of this property for thermal effects during the photodynamic process by MX-conjugated HGN were investigated. Material and Methods: After optimizing the synthesis of ultimate nanostructure, the characteristics of pharmacological agents including MX, HGN, methoxy polyethylene glycol (mPEG)-HGN, and MX-mPEG-HGN were determined. Then, the thermal response of MX was determined at 0-50° C. Finally, by applying light irradiation with a non-coherent source at a wavelength of 670 nm and exposures of 0 to 50 j/cm2, the profile release and temperature variation in MX-mPEG-HGN were determined. Results: The zeta potentials of HGN and MX were negative, which resulted in electrostatic repulsion between them. In order to solve this challenge, the surface modification of HGN with mPEG was performed, resulting in the chemical bonding of the drug with the nanostructures and increasing the stability of the final nanostructure. With increasing temperature, the optical density of the drug at 660 nm significantly increased, which is an effective induction of photodynamic effect. Conclusion: In this study, we used mPEG-HGN as the nanocarrier for MX. Also, the thermal behavior of MX was recognized as an important factor in increasing temperature that could improve the photodynamic process.

Background: MITOXANTRONE (MXT) is a drug for cancer therapy and a hazardous pharmaceutical to the environment which must be removed from contaminated waste streams. In this work, the removal of MXT by the electro-Fenton process over heterogeneous and homogenous catalysts is reported. Methods: The effects of the operational conditions (reaction medium pH, catalyst concentration and utilized current intensity) were studied. The applied electrodes were carbon cloth (CC) without any processing (homogenous process), graphene oxide (GO) coated carbon cloth (GO/CC) (homogenous process) and Fe3O4@GO nanocomposite coated carbon cloth (Fe3O4@GO/CC) (heterogeneous process). The characteristic properties of the electrodes were determined by atomic force microscopy (AFM), field emission scanning electron microscopy (FE-SEM) and cathode polarization. MXT concentrations were determined by using ultraviolet-visible (UV-Vis) spectrophotometer. Results: In a homogenous reaction, the high concentration of Fe catalyst (>0. 2 mM) decreased the MXT degradation rate. The results showed that the Fe3O4@GO/CC electrode included the most contact surface. The optimum operational conditions were pH 3. 0 and current intensity of 450 mA which resulted in the highest removal efficiency (96. 9%) over Fe3O4@GO/CC electrode in the heterogeneous process compared with the other two electrodes in a homogenous process. The kinetics of the MXT degradation was obtained as a pseudo-first order reaction. Conclusion: The results confirmed the high potential of the developed method to purify contaminated wastewaters by MXT.