Flupirtine, a re-discovered drug, revisited
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Inflammation Research
REVIEW
Flupirtine, a re-discovered drug, revisited Istvan Szelenyi
Received: 2 October 2012 / Revised: 20 December 2012 / Accepted: 2 January 2013 / Published online: 16 January 2013 Springer Basel 2013
Abstract Flupirtine was developed long before KV7 (KCNQ) channels were known. However, it was clear from the beginning that flupirtine is neither an opioid nor a nonsteroidal anti-inflammatory analgesic. Its unique muscle relaxing activity was discovered by serendipity. In the meantime, broad and intensive research has resulted in a partial clarification of its mode of action. Flupirtine is the first therapeutically used KV7 channel activator with additional GABAAergic mechanisms and thus the first representative of a novel class of analgesics. The presently accepted main mode of its action, potassium KV7 (KCNQ) channel activation, opens a series of further therapeutic possibilities. One of them has now been realized: its back-up compound, the bioisostere retigabine, has been approved for the treatment of epilepsy.
with skeletal muscle relaxing activity (Fig. 1). Flupirtine was developed between the 1970s and the 1990s by the former Chemiewerk Homburg, Frankfurt am Main, Germany, and its legal successors (renamed as Degussa Pharma Group and, after a merger, as ASTA Pharma and ASTA Medica). Most nonclinical pharmacodynamic studies conducted so far were performed under the responsibility of the research group located in Frankfurt am Main in close cooperation with its American partner Carter Wallace Laboratories, Cranbury, NJ, USA, under the leadership of Duane Sofia. Presently, flupirtine is marketed by TEVA and MEDA.
Keywords Analgesia Skeletal muscle relaxation Potassium channels GABA Retigabine
Searching for a novel analgesic in the 1960–1970s, the testing strategy of the German company was considerably different from those generally used in the last decades of the previous century. According to the then dominant pharmacodynamic principles, the screening procedure was mainly based on in-vivo investigations. The aim of the research in Frankfurt was to find centrally acting novel analgesics with mode(s) of action different from those of opiates. Consequently, newly synthesized compounds were screened and characterized on different animal models of nociception. In the mid-1980s, it became obvious that a novel analgesic could not be approved without an exact knowledge of its mode of action. For this reason, intensive research was begun into the possible mode(s) of action of flupirtine. Due to the chemistry-dominated research management, there was minimal understanding of more detailed electrophysiological and biochemical studies. These kinds of investigations were then performed in collaboration with external university institutes.
Introduction Flupirtine maleate (abbreviated as flupirtine) (internal code numbers: D-9998, W-2964M) is a unique analgesic agent
Responsible Editor: Michael Parnham. I. Szelenyi (&) Institute for Experimental and Clinical Pharmacology and Toxicology, Do
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