The Experts below are selected from a list of 198 Experts worldwide ranked by ideXlab platform
Guo Hong - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of Molecularly Imprinted Microspheres Polymer with 4-Aminopyridine as Template and the Study of Their Binding Characteristics
Chemical Research in Chinese Universities, 2020Co-Authors: Guo HongAbstract:The molecularly imprinted microspheres using 4 aminopyridine as template were prepared with precipitation polymerization. The batch way was used to investigate the selectively binding ability of the microspheres for 4 aminopyridine. The effects of different amount of solvent and initiator on the shape and the size of the particles were studied. The substrate selectivity of the polymer was investigated. The results showed that the imprinted polymer exhibited a high affinity for 4 aminopyridine among the tested compounds.
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Studies on the Binding Nature in Molecularly Imprinted Polymer Selective for 4-Aminopyridine
Chemical Research in Chinese Universities, 2020Co-Authors: Guo HongAbstract:A molecularly imprinted polymer was prepared using 4 aminopyridine as template. The bulk polymer obtained was ground up, sieved and investigated in equilibrium binding experiments to evaluate the binding characteristics of the 4 aminopyridine imprinted polymer. Scatchard analysis showed that two classes of binding sites were produced in the polymer matrix and their dissociation constants were calculated to be 6.0 μmol/L and 1.2 mmol/L respectively, by utilizing the model of multiple independent classes of binding sites. The substrate selectivity of the polymer was investigated. The results showed that the imprinted polymer exhibited much higher affinity for 4 aminopyridine among the tested compounds. \{ 1H NMR\} studies and the analysis of the resonance structure of 4 aminopyridine indicated that the selective binding interaction between the template and binding sites in the polymer arose from their ionic interaction.
J. C. Koetsier - One of the best experts on this subject based on the ideXlab platform.
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4-Aminopyridine Is Superior to 3,4-Diaminopyridine in the Treatment of Patients With Multiple Sclerosis
JAMA Neurology, 1994Co-Authors: C. H. Polman, F. W. Bertelsmann, R. De Waal, H.a.m. Van Diemen, B.m.j. Uitdehaag, A. C. Van Loenen, J. C. KoetsierAbstract:Objective: To compare the efficacy and toxicity of 4-Aminopyridine and 3,4-diaminopyridine in patients with multiple sclerosis. Design: Intervention study with a before-after design and a randomized, double-blind, crossover design. Setting: University referral center. Patients: Twenty-four patients with definite multiple sclerosis who had been treated in a previous clinical trial with 4-Aminopyridine. Interventions: Nonresponders to treatment with 4-Aminopyridine (14 patients) were treated with 3,4-diaminopyridine in a 4-week, open-label trial with doses up to 1.0 mg/kg of body weight (before-after design). Responders to treatment with 4-Aminopyridine (10 patients) participated in a comparative study of 6 weeks' duration with 4-Aminopyridine and 3,4-diaminopyridine according to a randomized, double-blind, double-crossover design. Main Outcome Measures: Neurophysiologic variables for nonresponders, neurologic functions and symptoms on a visual analogue scale for responders, and side effects for both groups. Results: Toxicity profiles of 4-Aminopyridine and 3,4-diaminopyridine were different, and systemic tolerability was reduced for 3,4-diaminopyridine. 4-Aminopyridine was more effective than 3,4-diaminopyridine, especially for ambulation, fatigue, and overall daily functioning. Conclusion: Our data suggest that, concerning both efficacy and side effects, 4-Aminopyridine is superior to 3,4-diaminopyridine in the treatment of patients with multiple sclerosis.
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4-Aminopyridine in the Treatment of Patients With Multiple Sclerosis: Long-term Efficacy and Safety
JAMA Neurology, 1994Co-Authors: C. H. Polman, F. W. Bertelsmann, A. C. Van Loenen, J. C. KoetsierAbstract:Objective: To study the long-term efficacy and safety of 4-Aminopyridine in patients with multiple sclerosis. Design: Case series, follow-up varying from 6 to 32 months. Setting: University referral center. Patients: Thirty-one patients with definite MS, 23 of them being exposed to long-term administration (6 to 32 months) of 4-Aminopyridine, since they showed a favorable initial response to the drug. Interventions: Long-term oral treatment with 4-Aminopyridine in daily doses of up to 0.5 mg/kg of body weight. Main Outcome Measures: Neurologic functions and symptoms as reported by the patients; side effects. Results: Twenty of 23 patients who showed a favorable initial response benefited from long-term administration. Ambulation and fatigue (each in 13 patients) and visual function (in five patients) were most frequently reported to be improved. Three major side effects did occur during a follow-up of 406 patient months: a generalized epileptic seizure in two patients and hepatitis in one. Conclusions: Although a substantial proportion of patients with multiple sclerosis seem to benefit from long-term administration of 4-Aminopyridine, additional studies are needed to clarify the exact value of the drug.
Yu Huang - One of the best experts on this subject based on the ideXlab platform.
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4-Aminopyridine-induced phasic contractions in rat caudal epididymis are mediated through release of noradrenaline.
European Journal of Pharmacology, 1995Co-Authors: Yu HuangAbstract:Abstract 4-Aminopyridine, a K+ channel blocker, evoked phasic contractions in the caudal duct of the rat epididymis. The 4-Aminopyridine-induced contractile response was either inhibited or prevented by the α1-adrenoceptor antagonists, prazosin (IC50 = 2.7 nM) and benoxathian (IC50 = 14.6 nM). Blockers (1 μM) of α2-adrenoceptors and purinoceptors but not of β-adrenoceptors or muscarinic receptors caused a small but statistically significant reduction of the 4-Aminopyridine-induced response. 4-Aminopyridine lost its ability to induce contractions after noradrenergic nerves had been destroyed by 6-hydroxydopamine. In addition, protriptyline and xylamine, blockers of noradrenaline uptake, also inhibited the 4-Aminopyridine-induced contractile response. However, other putative K+ channel blockers (tetraethylammonium ion, quinine, quinidine and glibenclamide) did not cause the muscle to contract. These findings demonstrate that the 4-Aminopyridine-induced release of noradrenaline and adenosine 5′-triphosphate as co-transmitters results from membrane depolarization due to 4-Aminopyridine blockade of K+ channels in noradrenergic nerve terminals. The 4-Aminopyridine-sensitive K+ channels might thus play a physiological role in regulating the nerve membrane potential and neurotransmission in the rat caudal epididymis.
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BaCl2‐ and 4‐aminopyridine‐evoked phasic contractions in the rat vas deferens
British Journal of Pharmacology, 1995Co-Authors: Yu HuangAbstract:1. The actions of BaCl2 and 4-Aminopyridine, blockers of K+ channels, on the mechanical activity of the epididymal half of the rat vas deferens were investigated. 2. Both BaCl2 and 4-Aminopyridine dose-dependently evoked phasic contractions. High extracellular potassium (35-40 mM) caused a tonic contraction but abolished the BaCl2- and 4-Aminopyridine-induced phasic activity and reduced the BaCl2-induced sustained component of contraction, but increased the 4-Aminopyridine-induced tonic contraction. 3. Omission of calcium from the extracellular medium totally abolished the 4-Aminopyridine-induced response but only reduced the mean amplitude of phasic contractions induced by BaCl. 4. Procaine (10 mM), an inhibitor of internal calcium release, completely abolished the phasic activity and reduced the sustained contraction induced by BaCl2. The remaining tone was abolished by nifedipine (1 microM). 5. Tetraethylammonium (1 mM) suppressed the amplitude of the BaCl2-induced phasic contractions, and induced a biphasic increase in tonic tension. 6. The BaCl2-induced responses were resistant to prazosin (1 microM), yohimbine (3 microM), propranolol (3 microM) or atropine (3 microM); in contrast, the 4-Aminopyridine-induced activity was effectively inhibited by prazosin (1 microM) attenuated by yohimbine (1 microM) and atropine (1 microM) but not by propranolol (3 microM). The 4-Aminopyridine-induced response was abolished by pretreatment of the vas deferens with 6-hydroxydopamine (0.5 mM). 7. The results indicate that the BaCl2-evoked activity in the vas deferens was mainly due to blockade of Ba(2+)-sensitive K+ channels on the smooth muscle plasma membrane. Subsequent calcium entry through the depolarized plasma membrane was needed to trigger generation of phasic contractions. 4-Aminopyridine-induced action, however, was largely mediated by neurotransmitters released from the depolarized nerve terminals as a result of blockade of K+ channels.
Ángel Martín Pendás - One of the best experts on this subject based on the ideXlab platform.
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On the impact of a phosphoryl group in the recognition capabilities of 2-aminopyridines toward carboxylic acids
Theoretical Chemistry Accounts, 2019Co-Authors: Miguel Gallegos, Sara Gil-guerrero, A. Fernández-alarcón, Diego Bouzas-ramos, Judith Martín, Carmen Concellón, J. M. Costa, R. Mendoza-meroño, S. García-granda, Ángel Martín PendásAbstract:Inspired by natural molecular recognition processes, many research efforts have been routed in recent years toward the design of new host–guest molecular systems based on non-covalent interactions. Within this field, 2-aminopyridines (2APs) have been widely studied due to their tunable spectroscopic response in the presence of carboxylic acids. Herein, we present and analyze a novel family of 2AP core compounds based on 2-phosphorylamidopyridine (2PAP). Linear response time-dependent density functional theory (TD-DFT) has been used to characterize and model several spectroscopic properties of 2PAP. Our results, validated through experiments, show that TD-DFT can provide a reliable description of the electronic excited states of these aromatic systems. In addition, we have also studied the amino–imino tautomerization of 2AP and 2PAP in light of TD-DFT tools. We show that the presence of a carboxylic acid has a catalytic effect on the tautomerization reaction, which otherwise does not occur spontaneously at room temperature. These results suggest that this low-cost computational approach can be applied to more complex organic systems derived from 2-aminopyridine, paving the way for the development of potentially useful sensing materials and organic species for molecular recognition.
Hans-peter Hartung - One of the best experts on this subject based on the ideXlab platform.
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Restoring Axonal Function with 4-Aminopyridine: Clinical Efficacy in Multiple Sclerosis and Beyond
CNS Drugs, 2018Co-Authors: Verena Isabell Leussink, Xavier Montalban, Hans-peter HartungAbstract:The oral potassium channel blocker 4-Aminopyridine has been used in various neurological conditions for decades. Numerous case reports and studies have supported its clinical efficacy in ameliorating the clinical presentation of certain neurological disorders. However, its short half-life, erratic drug levels, and safety-related dose restrictions limited its use as a self-compounded drug in clinical practice. This changed with the introduction of a prolonged-release formulation, which was successfully tested in patients with multiple sclerosis. It was fully approved by the US FDA in January 2010 but initially received only conditional approval from the European Medicines Agency (EMA) in July 2011. After additional clinical studies, this conditional approval was changed to unrestricted approval in August 2017. This article reviews and discusses these recent studies and places aminopyridines and their clinical utility into the context of a broader spectrum of neurological disorders, where clinical efficacy has been suggested. In 2010, prolonged-release 4-Aminopyridine became the first drug specifically licensed to improve walking in patients with multiple sclerosis. About one-third of patients across disease courses benefit from this treatment. In addition, various reports indicate clinical efficacy beyond multiple sclerosis, which may broaden its use in clinical practice.
