Pharmacological approaches for a novel GABAa receptor agonist: the long and winding road of drug development in anesthesia

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Although several intravenous anesthetic agents are used in daily clinical practice, the ideal anesthetic agent still does not exist (yet). In this PhD-thesis, various pharmacological approaches are used to investigate the novel anesthetic agent ABP-700 and to assess the extent to which it approaches the ideal anesthetic agent. In the first part of the thesis, its safety and clinical profile are assessed in a phase I clinical trial. ABP-700 seems to have various beneficial properties, as it provides hemodynamic and respiratory stability sometimes lacking in other anesthetic agents, and shows a fast on- and offset of clinical effect. However, one major side effect is the occurrence of involuntary muscle movements. The second part of the thesis zooms in on the origin of these muscle movements, which are seen in the use of other anesthetics as well. It could be concluded, that these movements are most likely not of an epileptic nature, but that they are more likely caused by a disequilibrium that occurs in the central nervous system during induction of anesthesia. This notion is supported by a pharmacokinetic-pharmacodynamic model that we developed, using the data that we gathered during the phase I trial. Also, it was observed that a certain intrinsic susceptibility for these muscle movements exists in certain subjects. In order to find out what this intrinsic susceptibility and the exact mechanism behind these movements are, further research is necessary.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Struys, Michel, Supervisor
    • Absalom, Tony, Supervisor
    • Eleveld, Douglas, Co-supervisor
    Award date25-Oct-2021
    Place of Publication[Groningen]
    Publisher
    DOIs
    Publication statusPublished - 2021

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