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  • 1
    ISSN: 1432-2129
    Keywords: Schlüsselwörterα2-Adrenozeptor-Agonisten: Clonidin ; Opioide: Morphin ; Lokalanästhetika: Bupivacain ; Anästhesietechnik: regional ; rückenmarksnah ; Pharmakologie: Interaktionen: additiv ; synergistisch ; Nozizeption ; Key wordsα2-Adrenoceptor agonists ; Opioids ; Local anaesthetics ; Regional anaesthesia ; Neuraxial anaesthesia ; Interactions ; Additive effect ; Synergistic effect ; Nociception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The interactions of α2-adrenoceptor agonists with anaesthetics, analgesics and local anaesthetics are not only of practical importance in many areas of anaesthesia and pain therapy, but also of significant theoretical interest. Laboratory investigations and animal research allow us to study the pharmacological mechanisms of these drug interactions by using the tools of molecular biology. This may lead to the establishment of a scientific basis allowing the definition of rational drug therapies. In the first part of this overview, recent data on local anaesthetic effects of α2-adrenoceptor agonists on peripheral nerve conduction and their interaction with local anaesthetics are presented. Some important experimental work focusing on additive and synergistic spinal interactions of α2-adrenoceptor agonists with opioids and some other agents are then discussed. Finally, there is a brief reference to the central role of the spinal cord in mediating and controlling nociception.
    Notes: Zusammenfassung Die Interaktionen der α2-Adrenozeptoragonisten mit Anästhetika, Analgetika und Lokalanästhetika sind nicht nur von praktischer Bedeutung für viele Bereiche der Anästhesie und Schmerztherapie, sondern auch von theoretischem Interesse, weil gerade im Laborexperiment und im Tierversuch wichtige molekularbiologische Mechanismen und physiologische Grundlagen der pharmakologischen Interaktionen untersucht und dargestellt werden können. In dieser Übersichtsarbeit werden Untersuchungen zu den lokalanästhetischen Effekten der α2-Adrenozeptoragonisten am peripheren Nerven und ihre Interaktionen mit Lokalanästhetika vorgestellt. Dann werden einige laborexperimentelle Arbeiten zusammengefaßt, in denen additive und supraadditive spinale Interaktionen von α2-Adrenozeptoragonisten mit Opioiden, Physostgimin, Carbachol, Adenosin, Midazolam und Ketorolac nachgewiesen werden konnten. Schließlich soll die zentrale Rolle des Rückenmarks im Rahmen der physiologischen Kontrolle der Nozizeption kurz diskutiert werden.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2013
    Keywords: K+ channels ; Ion permeation ; Chimeric K+ pore ; Single-site mutation ; Selectivity ; TEA blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A conservative reversion at position 374 in a chimeric K+ pore, CHM, switched the preferred ionic conductance from K+ to Rb+. To understand how selectivity was switched, codons for 18 different amino acids were substituted at position 374 in each of two different K+ channels CHM and Kv2.1, the host channel for CHM. After injection of cRNA into Xenopus oocytes, less than half of the substituted mutants expressed functional channels. In both CHM and Kv2.1, channels with the substituted hydrophobic residues Val or Ile expressed Rb+-preferring pores while channels with the substituted polar residues Thr or Ser expressed K+-preferring pores. Val or Ile stabilized while Thr or Ser destabilized blockade by internal tetraethylammonium (TEA) confirming the importance of hydrophobic interactions for blockade. TEA blockade was dependent upon the charge carrier and was more effective in the presence of the ion having the larger conductance. The results are consistent with a model in which the side chains at position 374 form a filter for K+ and Rb+ ions and a site for blockade by internal TEA.
    Type of Medium: Electronic Resource
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