Parkinson's disease is one of the most common neurodegenerative disorders world widely. Although curable therapies are practically not available yet, symptomatic managements using anti-Parkinson medications have shown to be quite effective to improve patients' quality of life. The discovery of dopaminergic deficits in Parkinson's disease in 1960s have brought about the human clinical trials of levodopa, which opened an “Era of Dopamine” in treatment history of the Parkinson's disease. Levodopa still remains gold standard. Dopamine agonists have proved their efficacies and delayed the development of long-term complications of levodopa use. Inhibitors of respective enzyme monoamine oxidase-B and catechol-O-methyltransferase, anticholinergics, and amantadine strengthen the therapeutic effects via either monotherapy or adjunctive way. Strategy of continuous dopaminergic stimulation and disease modification are weighing in current advances. This article is providing evidence-based review of pharmacological treatment of Parkinson's disease from early to advanced stages as well as management its unavoidable adverse reactions.
Amantadine ; Catechol O-Methyltransferase ; Cholinergic Antagonists ; Dopamine Agonists ; Drug Therapy ; Humans ; Levodopa ; Neurodegenerative Diseases ; Parkinson Disease ; Quality of Life ; Therapeutic Uses

OBJECTIVE: We examined whether amantadine can prevent the development of dyskinesia. METHODS: Patients with drug-naïve Parkinson's disease (PD), younger than 70 years of age and in the early stage of PD (Hoehn and Yahr scale < 3), were recruited from April 2011 to December 2014. The exclusion criteria included the previous use of antiparkinsonian medication, the presence of dyskinesia, significant psychological disorders, and previous history of a hypersensitivity reaction. Patients were consecutively assigned to one of 3 treatment groups in an open label fashion: Group A-1, amantadine first and then levodopa when needed; Group A-2, amantadine first, dopamine agonist when needed, and then levodopa; and Group B, dopamine agonist first and then levodopa when needed. The primary endpoint was the development of dyskinesia, which was analyzed by the Kaplan-Meier survival rate. RESULTS: A total of 80 patients were enrolled: Group A-1 (n = 27), Group A-2 (n = 27), and Group B (n = 26). Twenty-four patients were excluded from the analysis due to the following: withdrawal of amantadine or dopamine agonist (n = 9), alternative diagnosis (n = 2), withdrawal of consent (n = 1), and breach in the protocol (n = 12). After exclusion, 5 of the 56 (8.93%) patients developed dyskinesia. Patients in Group A-1 and A-2 tended to develop dyskinesia less often than those in Group B (cumulative survival rates of 0.933, 0.929, and 0.700 for A-1, A-2, and B, respectively; p = 0.453). CONCLUSION: Amantadine as an initial treatment may decrease the incidence of dyskinesia in patients with drug-naïve PD.
Amantadine ; Diagnosis ; Dopamine Agonists ; Dyskinesias ; Humans ; Hypersensitivity ; Incidence ; Levodopa ; Parkinson Disease ; Survival Rate

Nineteen highly pathogenic avian influenza (HPAI) H5N8 viruses were isolated from wild birds in the Donglim reservoir in Gochang, Jeonbuk province, Korea, which was first reported to be an outbreak site on January 17, 2014. Most genes from the nineteen viruses shared high nucleotide sequence identities (i.e., 99.7% to 100%). Phylogenetic analysis showed that these viruses were reassortants of the HPAI H5 subtype and the H4N2 strain and that their hemagglutinin clade was 2.3.4.4, which originated from Eastern China. The hemagglutinin protein contained Q222 and G224 at the receptor-binding site. Although the neuraminidase protein contained I314V and the matrix 2 protein contained an S31N substitution, other mutations resulting in oseltamivir and amantadine resistance were not detected. No substitutions associated with increased virulence and enhanced transmission in mammals were detected in the polymerase basic protein 2 (627E and 701D). Non-structural-1 was 237 amino acids long and had an ESEV motif with additional RGNKMAD amino acids in the C terminal region. These viruses caused deaths in the Baikal teal, which was unusual, and outbreaks occurred at the same time in both poultry and wild birds. These data are helpful for epidemiological understanding of HPAI and the design of prevention strategies.
Amantadine ; Amino Acids ; Animals ; Base Sequence ; Birds ; China ; Disease Outbreaks ; Hemagglutinins ; Influenza in Birds* ; Jeollabuk-do ; Korea* ; Mammals ; Neuraminidase ; Oseltamivir ; Poultry ; Virulence

OBJECTIVE: Guillain-Barre syndrome (GBS) is an acute post-infectious immune-mediated peripheral neuropathy with a variable clinical course and outcome. Identifying patients with poor outcome in the early stage might provide an opportunity for more effective and aggressive treatment and better prognosis. We aimed to determine early clinical factors associated with poor functional outcome in GBS. METHODS: Forty-seven patients with GBS were enrolled and followed up at Dongguk University Ilsan Hospital during May 2005–June 2015. Data collected retrospectively were used to identify risk factors of being unable to walk at 6 months. Potential predictors of poor outcome at 6 months were analyzed. RESULTS: Older age (≥55 years, P=0.002), low Medical Research Council (MRC) scale sum score (P=0.001), high GBS disability score (P=0.042), respiratory failure (P=0.042), severe weakness unable to walk (P=0.005), or voiding difficulty (P=0.001) at hospital ad-mission were associated with being unable to walk at 6 months. Preceding infections, subtype of acute motor axonal neuropathy (AMAN), and existence of GM1 antibody were not associated with poor prognosis in our study. CONCLUSION: Our study confirmed that the poor outcome is associated with older age, severity indicated by GBS disability score or MRC sum score, and ventilator support or walking disability at admission, but was not consistent with the previous literatures reporting preceding infection, AMAN subtype, and GM1 antibody as poor prognostic factors. Our study identified initial voiding difficulty as a novel poor prognostic factor, which implicates severe involvement of sacral roots.
Amantadine ; Axons ; Guillain-Barre Syndrome* ; Humans ; Peripheral Nervous System Diseases ; Prognosis ; Respiratory Insufficiency ; Retrospective Studies ; Risk Factors ; Ventilators, Mechanical ; Walking

This study sought to investigate the in vivo antiviral effect of amantadine (AM) and biphenyl dimethyl dicarboxylate (DDB) on hepatitis B virus (HBV) in HBV replication mice. HBV replication-competent plasmid was transferred into male BALB/c mice by using hydrodynamics-based in vivo transfection procedure to develop HBV replication mouse model. The model mice were matched by body weigh, age and serum levels of hepatitis B e antigen (HBeAg) and were divided into four groups: AM group, DDB group, AM+DDB group and NS group, with the last one as control, and the mice of each group were administered corresponding agent orally twice a day, in a medication course lasting 3 d. On the third day, the mice were sacrificed 4-6 h after the last oral intake. HBV DNA replication intermediates in liver were analyzed by Southern blot hybridization. The serum hepatitis B surface antigen (HBsAg) and HBeAg were detected by enzyme linked immunosorbent assay (ELISA). Compared to the animals in the control group, HBV DNA replication intermediates in liver and HBsAg and HBeAg in serum from the AM and AM plus DDB group of mice decreased, and there was no difference between these two groups of mice. The levels of HBV DNA intermediate from liver and the serum HBsAg and HBeAg between the control and DDB group, however, were not obviously different. In conclusion, the inhibition effect of AM on HBV was detected, but treatment with DDB for 3 days did not influence the viral replication and expression of HBV in the HBV replication mice.
Amantadine ; pharmacology ; Animals ; Antiviral Agents ; pharmacology ; DNA Replication ; DNA, Viral ; biosynthesis ; Dioxoles ; pharmacology ; Disease Models, Animal ; Hepatitis B ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; physiology ; Male ; Mice ; Mice, Inbred BALB C ; Plasmids ; Transfection ; Virus Replication ; drug effects

BACKGROUND AND PURPOSE: No previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barre syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance. METHODS: Serum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody. RESULTS: Among 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) by a single electrophysiological study. CONCLUSIONS: Anti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.
Amantadine ; Antibodies* ; Axons ; Cranial Nerves ; Facial Nerve ; Guillain-Barre Syndrome* ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Korea ; Male ; Ophthalmoplegia ; Prevalence*

This paper reports the establishment of a method for rapid identification 15 effective components of anti common cold medicine (paracetamol, aminophenazone, pseudoephedrine hydrochloride, methylephedrine hydrochloride, caffeine, amantadine hydrochloride, phenazone, guaifenesin, chlorphenamine maleate, dextromethorphen hydrobromide, diphenhydramine hydrochloride, promethazine hydrochloride, propyphenazone, benorilate and diclofenac sodium) with MRM by LC-MS/MS. The samples were extracted by methanol and were separated from a Altantis T3 column within 15 min with a gradient of acetonitrile-ammonium acetate (containing 0.25% glacial acetic acid), a tandem quadrupole mass spectrometer equipped with electrospray ionization source (ESI) was used in positive ion mode, and multiple reaction monitoring (MRM) was performed for qualitative analysis of these compounds. The minimum detectable quantity were 0.33-2.5 microg x kg(-1) of the 15 compounds. The method is simple, accurate and with good reproducibility for rapid identification many components in the same chromatographic condition, and provides a reference for qualitative analysis illegally added chemicals in anti common cold medicine.
Acetaminophen ; analysis ; Acetanilides ; analysis ; Amantadine ; analysis ; Aminopyrine ; analysis ; Anti-Inflammatory Agents, Non-Steroidal ; analysis ; Antipyretics ; analysis ; Antipyrine ; analogs & derivatives ; analysis ; Caffeine ; analysis ; Chlorpheniramine ; analysis ; Chromatography, Liquid ; Diclofenac ; analysis ; Diphenhydramine ; analysis ; Drug Contamination ; Drug Stability ; Ephedrine ; analogs & derivatives ; analysis ; Guaifenesin ; analysis ; Promethazine ; analysis ; Pseudoephedrine ; analysis ; Reproducibility of Results ; Salicylates ; analysis ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Influenza virus RNA-dependent RNA polymerase (RdRP) is essential for replication and expression of influenza virus genome. Viral genomic sequences encoding RdRP are highly conservative, thus making it a potential anti-influenza drug target. A cell-based influenza RdRP inhibitor screening assay was established by a luciferase reporter system to analyze the activity of RdRP. Specificity study and statistic analysis showed that the screening assay is sensitive and reproducible.
Amantadine ; pharmacology ; Antiviral Agents ; isolation & purification ; pharmacology ; Drug Evaluation, Preclinical ; methods ; Genes, Reporter ; HEK293 Cells ; Humans ; Influenzavirus A ; enzymology ; Luciferases ; genetics ; metabolism ; Oseltamivir ; pharmacology ; Plasmids ; RNA Replicase ; antagonists & inhibitors ; metabolism ; Reproducibility of Results ; Ribavirin ; pharmacology ; Sensitivity and Specificity ; Transfection ; Zanamivir ; pharmacology

Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic activity in the nervous system. It is characterized by a triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. Escitalopram is a selective serotonin reuptake inhibitor. Amantadine, an anti-influenza agent, is commonly used for the treatment of parkinsonism; it also has serotonergic activity. Amantadine can induce toxicity in patients with renal dysfunction because it is excreted mainly in the urine. We report a rare case of serotonin syndrome in a 73-year-old woman with Parkinson's disease, depression, and end-stage renal disease undergoing maintenance hemodialysis. She presented with confusion, myoclonus, and fever after starting escitalopram for her depression while on amantadine for parkinsonism. Based on this case, amantadine as well as escitalopram should be placed on the list of medications that can precipitate serotonin syndrome. The side effects of these drugs should be monitored, especially in end-stage renal disease.
Aged ; Amantadine ; Citalopram ; Depression ; Drug Toxicity ; Female ; Fever ; Humans ; Kidney Failure, Chronic ; Myoclonus ; Nervous System ; Parkinson Disease ; Parkinsonian Disorders ; Renal Dialysis ; Serotonin ; Serotonin Syndrome

BACKGROUND: The aim of the study was to describe the characteristics, treatments, and outcomes of critically ill patients with pandemic Influenza A/H1N1 2009 at a major medical center in Korea. METHODS: This retrospective observational study examined critically ill adult patients with pandemic Influenza A/H1N1 2009, who were admitted to the AMC between August and December 2009. RESULTS: 27 patients with confirmed pandemic Influenza A/H1N1 2009 were admitted to the intensive care unit (ICU) at the Asan Medical Center (AMC). The median age (IQR) was 59 years (41~67), and 66.7% of the patients were older than 51 years. A total of 81.5% of the patients had 2 or more co-morbidities. The median time (IQR) from symptom onset to presentation was 2 days (1~4), and the median time from presentation to ICU admission was 0 days (0~1.5). All patients received oseltamivir (300 mg/day) and 13 patients received triple combination therapy (oseltamivir, amantadine, ribavirin). Twelve patients required mechanical ventilation on the first day of ICU admission. A total of 6 patients (22.2%) died within 28 days of admission. The patients who died had significantly higher acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores at presentation. There were no significant differences in age, co-morbidities, or antiviral regimens between survivors and non-survivors. CONCLUSION: Critical illness related to pandemic Influenza A/H1N1 2009 was common in elderly patients with chronic co-morbidities. All patients were given high-dose oseltamivir or triple combination antiviral therapy. Nonetheless, patients with critical illnesses associated with pandemic Influenza A/H1N1 2009 had a death rate of 22.2%.
Adult ; Aged ; Amantadine ; APACHE ; Critical Illness ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; Intensive Care Units ; Korea ; Oseltamivir ; Pandemics ; Respiration, Artificial ; Retrospective Studies ; Survivors