Studies on the mechanism of action of amantadine.
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1 The effect of amantadine hydrochloride on various aspects of catecholamine metabolism in the rat brain has been investigated. 2 Amantadine failed to have any significant effect on brain concentrations of dopamine or noradrenaline even when administered daily for 9 days. 3 Amantadine had no effect on the rate of decline of noradrenaline and dopamine concentrations after alpha-methyl-p-tyrosine. 4 In vitro amantadine inhibited dopamine uptake into synaptosomes only at high concentrations, and caused little release of dopamine from synaptosomes. 5 There is no evidence from these results to suggest that the anti-Parkinsonian effect of amantadine is related to an action on dopaminergic mechanisms. (+info)
An Advisory Committee Statement (ACS). National Advisory Committee on Immunization (NACI). Statement on influenza vaccination for the 1998-1999 season.
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The National Advisory Committee on Immunization (NACI) provides Health Canada with ongoing and timely medical, scientific, and public-health advice relating to immunization. Health Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge, and is disseminating this document for information purposes. Persons administering or using the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the monograph(s) of the Canadian licensed manufacturer(s) of the vaccine(s). Manufacturer(s) have only sought approval of the vaccine(s) and provided evidence as to its safety and efficacy when used in accordance with the product monographs. (+info)
Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP).
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This report updates 1998 recommendations by the Advisory Committee on Immunization Practices (ACIP) on the use of influenza vaccine and antiviral agents (MMWR 1998;47[No. RR-6]:1-26). The principal changes include a) information on the influenza virus strains included in the 1999-2000 trivalent vaccine; b) discussion of the potential expanded use of influenza vaccine; c) new background information on live-attenuated influenza vaccines (LAIVs), neuraminidase-inhibitor drugs, and rapid diagnostic tests; d) new information on the epidemiology of influenza among travelers; and e) the addition of referenced citations. This report and other information on influenza can be accessed at the website for the Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC at . (+info)
Tetraethylammonium and amantadine identify distinct organic cation transporters in rat renal cortical proximal and distal tubules.
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Tetraethylammonium (TEA) and amantadine are two organic cations that are secreted by the kidney. It appears that each cation may characterize distinct renal tubule organic cation transport pathways. To test this hypothesis, we investigated the renal proximal and distal tubule energy-dependent transport properties of TEA and amantadine. Isolated tubules were incubated at 25 degrees C in bicarbonate buffer (Krebs-Henseleit solution) and nonbicarbonate buffer (Cross-Taggart) with varying concentrations of [14C]TEA or [3H]amantadine to determine initial rates of energy-dependent uptake of TEA and amantadine, respectively. The uptake of TEA could best be described by two transport sites, a high-affinity site and a lower affinity site. TEA uptake was not influenced by the presence of bicarbonate. Consistent with our previously reported data, amantadine uptake could also be described by two transport sites, a high-affinity-capacity site that is bicarbonate-dependent and a lower-affinity-capacity transport site that is bicarbonate-independent. The renal tubule uptake of amantadine into proximal and distal tubules, in Krebs-Henseleit solution or Cross-Taggart buffers, was not inhibited by 10 to 1000 microM of TEA. However, tubule accumulation of TEA could be inhibited (>90%) by amantadine in proximal and distal tubules in Krebs-Henseleit solution and Cross-Taggart buffers. In proximal tubules, N1-methylnicotinamide was not able to inhibit amantadine uptake but it reduced TEA uptake by 60 to 70% at similar concentrations. These data support the existence of multiple renal tubule organic cation transporters that have different substrate affinity and controlling mechanisms. It is also apparent that amantadine characterizes organic cation transporters that are distinct from those characterized by TEA. (+info)
In vivo analysis of amantadine renal clearance in the uninephrectomized rat: functional significance of in vitro bicarbonate-dependent amantadine renal tubule transport.
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Amantadine transport into renal proximal and distal tubules is bicarbonate dependent. In the present study, we addressed the effects of bicarbonate on renal clearance and urinary excretion of amantadine. Renal clearance of kynurenic acid was also studied to determine whether bicarbonate effects are specific for organic base transport by the kidney. After a moderate diuresis was established, animals received i.v. [(3)H]amantadine or [(3)H]kynurenic acid followed by an acute dose of sodium bicarbonate or physiological saline. Urine and blood samples were analyzed for [(3)H]amantadine or [(3)H]kynurenic acid, blood gases, and pH. Amantadine and kynurenic acid were excreted by the kidneys, and both compounds underwent renal tubular secretion. Amantadine metabolism occurred, and one metabolite was detected in the urine. In the bicarbonate-treated rats, the total amount of amantadine excreted in the urine was decreased, whereas the amount of metabolite recovered was similar in both groups. Bicarbonate treatment caused a sustained increase in blood bicarbonate levels, a mild increase in blood pH, and a decrease in amantadine renal clearance and in the amantadine/creatinine clearance ratio. Only a transient decrease in the renal clearance of kynurenic acid and the kynurenic acid/creatinine clearance ratio was observed. This study demonstrates that short-term changes in bicarbonate concentration may have significant effects on renal organic cation elimination. Coupled with our previous in vitro demonstration of bicarbonate-dependent organic cation transport, the present study suggests that bicarbonate inhibition of renal tubule organic cation secretion may explain the previous observation that bicarbonate dosing decreases amantadine excretion by the kidney. (+info)
New experimental and clinical data on leukaemia immunotherapy.
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The present results of our treatment of acute lymphoid leukaemia patients are summarized: 7 out of 20 randomized patients given active immunotherapy after chemoradiotherapy are still in complete remission after periods varying from seven to ten years (compared to none in the control group). The actuarial results on 100 patients show remission and survival curves presenting a plateau between three and five years for a certain percentage, suggesting a possible cure. Several parameters studied in 200 patients indicate that the factors affecting this percentage are age, cytological type, volume of the tumour, and the localization of leukaemic cells in certain areas. Experiments with L1210 leukaemia show that immunotherapy enhances the effect of chemotherapy when administered after chemotherapy but decreases it when administered before, which is in favour of the use of the sequence chemotherapy-immunotherapy clinically. (+info)
Amantadine and rimantadine have no direct inhibitory effects against hepatitis C viral protease, helicase, ATPase, polymerase, and internal ribosomal entry site-mediated translation.
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Amantadine, a drug known to inhibit influenza A viral matrix (M2) protein function, was reported to be an effective treatment in some patients with chronic hepatitis C virus (HCV) infection. Sequence comparison shows no homology between M2 and any of the HCV proteins. The effects of amantadine and a related analogue, rimantadine, on viral protease, helicase, ATPase, RNA-dependent RNA polymerase, and HCV internal ribosomal entry site (IRES) translation were tested by established in vitro biochemical assays. No inhibition (>15%) of HCV protease, helicase, ATPase, and polymerase was observed with concentrations up to 400 microgram/mL. IRES-specific inhibition was not observed at clinically relevant concentrations, but both cap and IRES reporter genes were suppressed at higher levels, suggesting nonspecific translation inhibition. In conclusion, amantadine and rimantadine have no direct and specific inhibitory effects against HCV protease, helicase, ATPase, polymerase, and IRES in vitro. (+info)
Laboratory characteristics of an attenuated influenza type A (H3N2) virus ('Alice' strain).
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The Alice strain of live attenuated influenza virus was obtained by selection of a gamma inhibitor-resistant strain from a virus recombinant between A/PR/8/34 (HON1) and A/England/42/72 (H3N2). Its behaviour in vitro and in vivo was studied. Three marker systems were investigated: resistance to serum inhibitors, growth capacity at high temperature and low sensitivity to amantadine hydrochloride. In ferrets the strain was found to be attenuated and immunogenic. Passages in man, animals and eggs have not affected its resistance to gamma inhibitors. (+info)