Amantadine HCl Research Articles

Genotoxic effect of Tamiflu and Adamine on DNA content in male albino mice

BackgroundTamiflu (Oseltamivir) and Adamine (Amantadine HCl) are antiviral drugs which are used for prevention and treatment for influenza. The present study was carried out to evaluate the effect of Tamiflu and Adamine on DNA content of hepatocytes of adult male albino mice.ResultsThe results of comet assay showed that treatment with Tamiflu and Adamine significantly increased (P < 0.005) the mean of DNA damage in hepatocytes of the treated mice in time dependent manner compared to control one. However qRT-PCR analysis showed the mRNA expression of BAX in mice liver of all treated groups with Adamine was significantly increased (P < 0.05) after ten days of treatment while the same gene was significantly decreased in Tamiflu treated group after ten days compared to control one, While the treatment of mice with both drugs simultaneously showed a significant increase (P < 0.05) in expression of BCL-2 gene and a decrease in expression of BAX gene after fifteen days of treatment.ConclusionTamiflu and Adamine had produced deleterious impacts on DNA content of hepatocytes of treated mice. Whereas, the results of treatments with Adamine indicated pathogenic impacts more than that induced by Tamiflu.

Repurposing of US-FDA approved drugs against SARS-CoV-2 main protease (Mpro) by using STD-NMR spectroscopy, in silico studies and antiviral assays

SARS-CoV-2 Main protease (Mpro) is a well-known drug target against SARS-CoV-2 infection. Identification of Mpro inhibitors is vigorously pursued due to its crucial role in viral replication. The present study was aimed to identify Mpro inhibitors via repurposing of US-FDA approved drugs by STD-NMR spectroscopy. In this study, 156 drugs and natural compounds were evaluated against Mpro. Among them, 10 drugs were found to be interacting with Mpro, including diltiazem HCl (1), mefenamic acid (2), losartan potassium (3), mexiletine HCl (4), glaucine HBr (5), trimebutine maleate (6), flurbiprofen (7), amantadine HCl (8), dextromethorphan (9), and lobeline HCl (10) in STD-NMR spectroscopy. Their interactions were compared with three standards (Repurposed anti-viral drugs), dexamethasone, chloroquine phosphate, and remdesivir. Thermal stability of Mpro and dissociation constant (Kd) of six interacting drugs were also determined using DSF. RMSD plots in MD simulation studies showed the formation of stable protein-ligand complexes. They were further examined for their antiviral activity by plaque reduction assay against SARS-CoV-2, which showed 55–100% reduction in viral plaques. This study demonstrates the importance of drug repurposing against emerging and neglected diseases. This study also exhibits successful application of STD-NMR spectroscopy combined with plaque reduction assay in rapid identification of potential anti-viral agents.

Effects of Tamiflu and Adamine on histology and ultrastructure of the liver of albino mice

BackgroundTamiflu (Oseltamivir) and Adamine (Amantadine HCl) are antiviral drugs which are used for prevention and treatment for influenza. The present study was carried out to evaluate the effect of Tamiflu and Adamine on the liver of adult male albino mice from the histological and ultrastructural points of views.ResultsHistological examination of liver sections treated with Tamiflu and Adamine included enlargement and congestion of central and hepatic veins in addition to erosion of their endothelial lining cells, cytoplasmic vacuolation of hepatocytes, pyknosis of their nuclei, and dilatation of hepatic sinusoid. The electron microscopic investigation illustrated mitochondrial swelling, fragmented rough endoplasmic reticulum, cytoplasmic vacuolation, the nuclei with irregular envelope and condensed heterochromatin, dilated microvilli in sinusoid, in addition to active Kupffer cells have many lysosomes and filopodia in its membrane.ConclusionThe study suggested that both drugs induced histopathological and ultrastructural alterations in hepatic tissue. In conclusion, Tamiflu and Adamine have pathological effects on liver of albino mice (Mus musculus).

Treating Comorbid Childhood Bipolar Disorder and ADHD

Pediatric mania is difficult to distinguish from childhood hyperactivity. Both share 3 common symptoms: distractibility, motoric hyperactivity, and talkativeness. Oftentimes, children are referred from their pediatrician due to a lack of appropriate response to stimulant medication. Pediatricians have learned that merely raising the dose or changing the stimulant does not work. A thorough neuropsychological evaluation often reveals bipolar mania. They may have comorbid bipolar disorder and ADHD. This poster paper will examine measures that can assist in this important differential diagnosis as well as offer treatment options, including medication management. This case study includes three pediatric patients diagnosed with childhood bipolar disorder and ADHD. A comprehensive psychoeducational assessment was conducted for each of the patients, which resulted in this comorbid diagnosis. One of the most helpful measures was the TOVA (i.e., Test of Variables of Attention). When a child's attention and impulsivity scores are normal, and response time and variability scores are abnormal, both on and off medication, that is an indication of a mood disorder, These children also performed poorly on measures of processing speed, and verbal learning and interference tasks. Measures of affect and personality were important diagnostically. A combination of amantadine and either clonidine HCL ER or propranolol, as prescribed by a medical psychologist, were found to be effective in controlling the symptoms of this comorbid diagnosis. An evaluation of children's intellectual, attentional, behavioral, mood, and personality functioning is crucial for a differential diagnosis. In cases of comorbidity, ADHD and childhood bipolar disorder, the sooner the child is on appropriate medications, the better. When just the surface diagnosis of ADHD is medicated, the outcome is often problematic. There may be a poor response to treatment and a higher rate of suicide.

132 Treating Comorbid Childhood Bipolar Disorder and ADHD

According to Nemeth et al. (2011), pediatric mania is difficult to distinguish from childhood hyperactivity. Both share 3 common symptoms: distractibility, motoric hyperactivity, and talkativeness (Biederman, 2000). Oftentimes, children are referred from their pediatrician due to a lack of appropriate response to stimulant medication. Pediatricians have learned that merely raising the dose or changing the stimulant does not work. A thorough neuropsychological evaluation often reveals Bipolar Mania. They may have comorbid Bipolar Disorder and ADHD. This poster paper will examine measures that can assist in this important differential diagnosis as well as offer treatment options, including medication management. This case study includes three pediatric patients diagnosed with Childhood Bipolar Disorder and ADHD. A comprehensive psychoeducational assessment was conducted for each of the patients, which resulted in this comorbid diagnosis. One of the most helpful measures was the TOVA. When a child's attention and impulsivity scores are normal, and response time and variability scores are abnormal, both on and off medication, that is an indication of a mood disorder (Nemeth et al., 2007). These children also performed poorly on measures of processing speed, and verbal learning and interference tasks (Henin et al., 2007). Measures of affect and personality were important diagnostically. A combination of Amantadine and either Clonidine HCL ER or Propranolol, as prescribed by a medical psychologist, were found to be effective in controlling the symptoms of this comorbid diagnosis. An evaluation of children's intellectual, attentional, behavioral, mood, and personality functioning is crucial for a differential diagnosis. In cases of comorbidity, ADHD and Childhood Bipolar Disorder, the sooner the child is on appropriate medications, the better. When just the surface diagnosis of ADHD is medicated, the outcome is often problematic. There may be a poor response to treatment and a higher rate of suicide.

Parkinson's Patients with Dyskinesia Switched from Immediate Release Amantadine to Open-label ADS-5102.

BackgroundADS‐5102 (amantadine) extended release capsules (GOCOVRI™) are a treatment for dyskinesia in patients with Parkinson's disease (PD). ADS‐5102 reduced dyskinesia and OFF time in phase 3 controlled trials of up to six months. Amantadine immediate release (IR) is used for dyskinesia, but suboptimal durability and tolerability limit its clinical utility.MethodsIn an ongoing, open‐label, phase 3 study in the US and Western Europe (NCT02202551), patients with PD received 274 mg of ADS‐5102 (equivalent to 340 mg amantadine HCl) once daily at bedtime for up to two years. Study outcomes included safety and assessment of motor complications, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part IV. This manuscript focuses on those patients switched to ADS‐5102 from amantadine IR. Results in two groups of patients who previously completed a randomized controlled trial (EASE LID or EASE LID 3) are also presented according to use of ADS‐5102 or placebo in that study before enrollment in the open‐label study.ResultsChange in MDS‐UPDRS Part IV at week 8 was –0.3 in the previous ADS‐5102 subgroup (n = 61), –3.4 in the previous placebo subgroup (n = 79), and –3.4 in the previous amantadine IR subgroup (n = 32). Effects were maintained to week 64. In the previous amantadine IR subgroup (mean treatment duration, 2.5 years), mean amantadine IR dose was 221 mg. Safety data were consistent with previous randomized controlled trials of ADS‐5102.ConclusionThese open‐label data suggest ADS‐5102 provides incremental reduction from baseline in MDS‐UDPRS Part IV score in patients switched directly from amantadine IR, without exacerbating adverse events.

Green in-Line Ion Selective Electrode Potentiometric Method for Determination of Amantadine in Dissolution Media and in Pharmaceutical Formulations

Amantadine HCl (AMN) is a well-known antiviral agent. Chemically, AMN chromophore privation leads to the absence of UV-absorbance, a condition that hinders direct spectrophotometric or simple chromatographic determination using common detectors without prior derivatization steps. In this work, an environmentally friendly ion selective electrode (ISE) method was developed for the determination of AMN, and measurements were carried out directly in the aqueous solution of the sample without pretreatment or derivatization steps. PVC-membranes were fabricated using nitrophenyl octyl ether as a plasticizer along with different cation exchangers, responses were compared, and that containing phosphomolybdic acid proved to have the best near-Nernstian slope through a wide linear range (4.57 × 10–7)–(1.0 × 10–2) M. The ion pair was obtained by soaking the membrane sensor in a 1 × 10–2 M solution of AMN. The sensor was able to determine AMN in colored and turbid solutions of its tablets and capsules without prior ex...

Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study).

ADS‐5102 is a long‐acting, extended‐release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS‐5102 in Parkinson's disease (PD) patients with levodopa‐induced dyskinesia. This was a randomized, double‐blind, placebo‐controlled, parallel‐group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS‐5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS‐5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ‐39). ADS‐5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P = 0.005). In addition, ADS‐5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P = 0.004), 340 mg (P = 0.008) and 420 mg (P = 0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260‐mg, 340‐mg, and 420‐mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260‐mg, 340‐mg, and 420‐mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS‐5102 was generally well tolerated and resulted in significant and dose‐dependent improvements in dyskinesia in PD patients. © 2015 Adamas Pharmaceuticals, Inc. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Safety and Efficacy Study of ADS-5102 (Amantadine HCl) Extended Release Capsules in Levodopa-Induced Dyskinesia (EASED Study) (P4.053)

Safety and Efficacy Study of ADS-5102 (Amantadine HCl) Extended Release Capsules in Levodopa-Induced Dyskinesia (EASED Study) (P4.053)

Rapid and convenient assays to assess potential inhibitory activity on in vitro hepatitis A replication

Three different antiviral assays were developed for the in vitro screening of inhibitors of the hepatitis A virus (HAV) of which (i) a cytopathic effect reduction assay suitable for medium-to-high-throughput screening and (ii) two virus yield reduction assays (based on quantification of viral RNA) for genotypes IB and IIIA. The assays were validated for antiviral studies with interferon-alpha (IFNα) and amantadine HCl, two known inhibitors of HAV replication. IFNα effectively inhibited HAV replication, whereas the activity of amantadine HCl appeared to be strain-dependent. Employing these assays, we assessed the effect of the known enterovirus inhibitors pleconaril, rupintrivir and enviroxime on HAV replication. Pleconaril exhibited some very moderate activity, the effect of rupintrivir proved to be strain-dependent. Enviroxime did not inhibit HAV replication, suggesting that phosphatidylinositol-4-kinase IIIβ is not crucial in the HAV life cycle.

Pharmacokinetics of amantadine in cats

This study reports the pharmacokinetics of amantadine in cats, after both i.v. and oral administration. Six healthy adult domestic shorthair female cats were used. Amantadine HCl (5 mg/kg, equivalent to 4 mg/kg amantadine base) was administered either intravenously or orally in a crossover randomized design. Blood samples were collected immediately prior to amantadine administration, and at various times up to 1440 min following intravenous, or up to 2880 min following oral administration. Plasma amantadine concentrations were determined by liquid chromatography-mass spectrometry, and plasma amantadine concentration-time data were fitted to compartmental models. A two-compartment model with elimination from the central compartment best described the disposition of amantadine administered intravenously in cats, and a one-compartment model best described the disposition of oral amantadine in cats. After i.v. administration, the apparent volume of distribution of the central compartment and apparent volume of distribution at steady-state [mean ± SEM (range)], and the clearance and terminal half-life [harmonic mean ± jackknife pseudo-SD (range)] were 1.5 ± 0.3 (0.7-2.5) L/kg, 4.3 ± 0.2 (3.7-5.0) L/kg, 8.2 ± 2.1 (5.9-11.4) mL·min/kg, and 348 ± 49 (307-465) min, respectively. Systemic availability [mean ± SEM (range)] and terminal half-life after oral administration [harmonic mean ± jackknife pseudo-SD (range)] were 130 ± 11 (86-160)% and 324 ± 41 (277-381) min, respectively.

Extractive-spectrophotometric methods for determination of anti-Parkinsonian drug in pharmaceutical formulations and in biological samples using sulphonphthalein acid dyes

A simple, accurate and highly sensitive spectrophotometric methods are proposed for the rapid and accurate determination of amantadine HCl (AMD) using bromocressol green (BCG), bromophenol blue (BPB) and bromothymol blue (BTB). The developed methods involve formation of stable yellow colored chloroform extractable ion-associate complexes of the amino derivative (basic nitrogen) of the AMD with three sulphonphthalein acid dyes, namely; BCG, BPB and BTB, in acidic medium. The ion-associates exhibit absorption maxima at 415, 412 and 414nm for BCG, BPB and BTB, respectively. AMD can be determined up to 1.5–16.5, 1.4–14.0 and 1.6–17μgmL−1, respectively. The effect of optimum conditions via acidity, reagent concentration, time, and solvent was studied. The stoichiometry of the reaction was found to be 1:1 in all cases. The low relative standard deviation values indicate good precision and high recovery values. These methods have been successfully applied for the assay of AMD in pharmaceutical formulations. Statistical comparison of the results with the reference method shows excellent agreement and indicates no significant difference in accuracy and precision.

Spectrophotometric microdetermination of anti-Parkinsonian and antiviral drug amantadine HCl in pure and in dosage forms

Two simple, rapid, sensitive, low-cost, and accurate methods (A and B) for the microdetermination of amantadine HCl (AMD) in pure form and in pharmaceutical formulations are developed. Method A is based on the formation of tris (o-phenanthroline)-iron(II) complex (ferroin) upon reaction of amantadine HCl with an iron (III)-o-phenanthroline mixture in sodium acetate-acetic acid buffer media. The ferroin complex is spectrophotometrically measured at λmax 509nm against reagent blank. Method B is based on the reduction of Fe (III) by the drug which forms colored complex (λmax 521nm) with 2,2′-bipyridyl. Optimizations of the experimental conditions are described. Beer’s law is obeyed in the concentration ranges 0.4–10 and 0.6–22μgmL−1 using 1,10-phenanthroline and 2,2′-bipyridyl, respectively. The developed methods have been successfully applied for the determination of AMD in bulk drugs and in pharmaceutical formulations. The common excipients and additives did not interfere in their determinations.

Toxic corneal oedema associated with amantadine use

Amantadine HCl is an antiviral agent used to treat and prevent influenza A. It is also indicated for the treatment of Parkinsonism and drug-induced extrapyramidal symptoms.[1] Off-label uses include multiple...

Bromocriptine blood levels after the concomitant administration of levodopa, amantadine and biperiden in Parkinson's disease

We recently demonstrated that when different drugs (mainly used for the treatment of Parkinson's disease) are administered in combination they interfere with the availability of bromocriptine in the brain of rats (striatum and hypothalamus). In the present study performed with parkinsonian patients, we measured plasma levels of bromocriptine (RIA) over 4 h after giving orally 5 mg bromocriptine alone; together with levodopa 250 mg plus 25 mg DCI (10 patients); with 100 mg amantadine HCl (5 patients) and with biperiden 5 mg (5 patients). Amantadine and biperiden did not interfere with the pharmacokinetics of bromocriptine. However, levodopa significantly diminished plasma levels (a mean increment of 1.78 mg +/- 0.30 vs 0.92 +/- 0.18 mg/ml). We postulate that levodopa may interfere with the metabolism of bromocriptine in the liver. Although we did not observe substantial clinical differences among the patients (Webster scale), this study supports our previous findings and suggests that one of the advantages of combined treatment may result from a modification of the plasma levels of bromocriptine by levodopa. A "smoothing" of the plasma bromocriptine curve possibly avoids sudden oscillations of the drug availability and enables a more "stable" penetrability of the medication into the central nervous system.

Simple and sensitive spectrophotometric methods for determination of amantadine hydrochloride

Three simple and sensitive spectrophotometric methods (A–C) for determination of amantadine hydro-chloride have been developed and validated. The first method (A) is based on the oxidation of the drug by ammonium molybdate. The second method (B) was based on the charge-transfer complexation reaction between the amantadine base as an electron donor and iodine as a σ-acceptor. The third method (C) is based on the reaction of N-alkylvinylamine formed from the interaction of the free amino group in amantadine molecule and acetalde-hyde with chloranil to give colored vinylamino-substituted benzoquinone. The colored products of these reactions were measured at their corresponding maximum absorption peaks. Different variables affecting the reactions were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients 0.9993–0.9998 were found between the reading and the corresponding concentration of the drug in the range 2–90 µg·ml−1. The limits of detection ranged from 0.16 to 1.91 µg·ml−1. The precision of the methods was satisfactory: the values of relative standard deviation did not exceed 1.63%. The proposed methods were successfully applied to the analysis of amantadine HCl in its capsules with good accuracy and precision; the label claim percentages ranged from 99.8 to 100.5 ± (0.52–1.22) %. The results obtained by the proposed spectrophotometric methods were comparable with those obtained by the official method.

Interferon induction treatment with and without amantadine HCl (AHCl) in patients with chronic hepatitis C

Interferon induction treatment with and without amantadine HCl (AHCl) in patients with chronic hepatitis C

Influenza virus genetics

Significant progress has been made in understanding the process of influenza A virus replication in cell culture; however, much less is known about the genetic control of virus-host interactions in disease. This review provides an overview of the genetic analysis of influenza virus biology. The functional map of the individual genes of influenza A virus is presented as well as the status of our current understanding of pathogenesis. Influenza has a segmented genome so it is possible to obtain reassortants that contain novel combinations of genome segments derived from different viruses. This is a very useful genetic tool and is also an important aspect of influenza evolution and biology. Human influenza viruses originate from avian strains of influenza virus so that influenza infection is at its basis a zoonosis. Influenza virus strains are host-restricted, however, and avian strains must be adapted to the human host. So questions of host-range and interaction with host factors are important determinants of the ability of influenza virus to cause disease in humans. Host-range is restricted primarily due to host-specific interactions of the ribonucleocapsid and the viral receptor. There are two classes of drugs for inhibiting influenza infection, amantadine HCl and neuraminidase inhibitors. The mode of action and basis for resistance to these drugs are presented. Prospective targets for antiviral therapy are also discussed.

Amantadine monotherapy of chronic hepatitis C patients infected with genotype lb.

We aimed to test the efficacy of amantadine in chronic hepatitis C (CHC) patients infected with genotype b. Twenty patients completed treatment with amantadine HCl, 100 mg b.i.d., for 6 months. Non-sustained biochemical improvement was observed without loss of HCV-RNA. We conclude that amantadine monotherapy is not effective in CHC.

SPECTROPHOTOMETRIC DETERMINATION OF AMANTADINE HYDROCHLORIDE IN CAPSULES

Amantadine HCl is used as an antiviral and an antiparkinson drug. We described spectrophotometric determination of amantadine HCl by derivatization with sodium 1,2-naphtoquinone-4-sulfonate in aqueous medium. The structure of the derivative was determined by IR, H1-NMR and mass spectral methods. The derivative was obtained quantitatively at pH 10 and 60 °C in 30 minutes and showed maximum absorption at 451 nm. The calibration curve obeys Beers's Law in the 5-25 mcg/ml range. The proposed method was applied to the determination of amantadine HCl in pharmaceutical dosage form (capsule). The results were statistically compared with USP XXIII procedure. Keywords: Amantadine HCl, spectrophotometric determination, 1,2- naphtoquinone-4-sulphonic acid.