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Chemical Compound Review

Pymadine     pyridin-4-amine

Synonyms: Fampridine-SR, Fampridine SR, VMI-103, VMI103, VMI 103, ...
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Disease relevance of 4-aminopyridine

  • These data indicate that NMDA-mediated ictal discharges induced by 4AP originate in the entorhinal cortex; such a conclusion is in line with clinical evidence obtained in temporal lobe epilepsy patients [1].
  • We conclude that at least some patients with acquired neuromyotonia have antibodies directed against aminopyridine- or alpha-dendrotoxin-sensitive K+ channels in motor and sensory neurons, and they are likely to be implicated in the disease process [2].
  • A crossover comparison of the two agents suggested that AP produces more central nervous system side effects (dizziness and confusion), whereas DAP produces more peripheral side effects (paresthesias and abdominal pain) [3].
  • OBJECTIVE: To evaluate the efficacy of 4-aminopyridine sustained release (4AP SR) (fampridine, EL-970) using quantitative measures of motor function in multiple sclerosis (MS) patients [4].
  • Through a combination of iterative medicinal chemistry and X-ray crystal structure based design, one of these leads was developed into the novel aminopyridine derivative 9, a low micromolar inhibitor of FabI from S. aureus (IC(50) = 2.4 microM) and Haemophilus influenzae (IC(50) = 4.2 microM) [5].

Psychiatry related information on 4-aminopyridine


High impact information on 4-aminopyridine

  • In hippocampal neurons, a slowly inactivating aminopyridine-sensitive transient potassium current, D-current, influences the time course of action potential repolarization and therefore activity-dependent Ca2+ entry [7].
  • Preliminary studies of AP demonstrated benefit in many temperature-sensitive patients with MS, and improvement of function was found in a large randomized double-blind, placebo-controlled crossover trial of 3 months of oral treatment in 68 patients with MS [3].
  • An aminopyridine dimer serves as a model for Watson-Crick base pairs, where similar reactions have been predicted by theory [8].
  • Aminopyridine block of Kv1.1 potassium channels expressed in mammalian cells and Xenopus oocytes [9].
  • Rather, the data are consistent with a simple binding scheme incorporating no changes in gating kinetics which conceives of aminopyridine molecules binding to closed K channels and being released from open channels in a voltage-dependent manner [10].

Chemical compound and disease context of 4-aminopyridine


Biological context of 4-aminopyridine

  • Each compound occupies the same region of the active site and projects an aminopyridine, a central hydrophobic group, and an aryl group, into the S1, S2, and aryl subsites on thrombin [14].
  • The benzoxazole 49, a cyclic analogue of 16, was a very potent enhancer of insulin sensitivity, and by modification of the aromatic heterocycle, an aminopyridine, 37, was identified as a lead compound from SAR studies [15].
  • A transient, low-threshold K+ current, which was 4AP sensitive and showed significant steady-state inactivation in the physiological membrane potential range (-40 to -60 mV), was evoked from a holding potential of -100 mV [16].
  • Large potassium signals and slow potentials evoked during aminopyridine or barium superfusion in cat cerebellum [17].
  • Studies of 7 beta-[2-(aminoaryl)acetamido]-cephalosporin derivatives. I. Synthesis and structure-activity relationships in the aminopyridine series [18].

Anatomical context of 4-aminopyridine


Associations of 4-aminopyridine with other chemical compounds

  • PURPOSE: We determined how CA3-driven interictal discharges block ictal activity generated in the entorhinal cortex during bath application of 4-aminopyridine (4AP, 50 microM) [24].
  • RESULTS: 4AP induced N-methyl-d-aspartate (NMDA) receptor-dependent ictal discharges that originated in the entorhinal cortex, disappeared over time, but were reestablished by cutting the Schaffer collateral (n = 20) or by depressing CA3 network excitability with local application of glutamatergic receptor antagonists (n = 5) [24].
  • Electrical stimulation (Schaffer collaterals and stratum oriens) combined with different aminopyridine compounds (AP) were used for neuronal activation [25].
  • It was also resistant to inactivation with periodate-oxidized aminopyridine adenine dinucleotide phosphate, an affinity label for malic enzyme [26].
  • N,N'-Dimethyl-N,N'-bis[(4-amidylphenyl)aminocarbonyl]-2,6-di aminopyridine (1) and 1,3-bis[5-(glycylamino)pyrid-2-yl]urea (3) showed remarkable DNA-binding abilities as determined by ultrafiltration assay using calf thymus DNA, their potencies being equal to and half that of netropsin, respectively [27].

Gene context of 4-aminopyridine


Analytical, diagnostic and therapeutic context of 4-aminopyridine

  • Electrical stimulation combined with application of aminopyridine compounds led to electron dense deposits of 60-400 nm diameter, mainly restricted to the activated input layers [25].
  • An aminopyridine-sensitive, early outward current recorded in vivo in neurons of the precruciate cortex of cats using single-electrode voltage-clamp techniques [31].
  • Plasma concentration profiles of the K+ channel-blocking compound Fampridine were obtained from (1) control subjects (n = 6) following oral administration of doses of 10, 15, 20, and 25 mg and (2) patients with spinal cord injury (SCI) (n = 11) following a single oral dose of 10 mg of an immediate-release formulation [32].
  • Elan has used its Intestinal Protective Drug Absorption System (IPDAS) drug delivery system to produce Neurelan, which is a controlled-release (twice daily) formulation of fampridine [223736] [33].


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