G. Schuster, M. Schwarz, F. Block
Jun 1, 1998
Citations
4
Influential Citations
22
Citations
Quality indicators
Journal
Cns Drug Reviews
Abstract
Flupirtine is a centrally acting non-opioid analgesic; it has been in clinical use since 1984. The pharmacological and therapeutic properties of flupirtine in pain states have been reviewed extensively (7). The present review addresses new and challenging data that have been published during recent years. In particular, it has been discovered that flupirtine, in a clinically relevant dosage range, has potent cytoand neuroprotective potential as well as anticonvulsant, and myorelaxant effects. Flupirtine reverses akinesia and rigidity in dopamine-depleted animals. These findings, and the reported reversal of N-methyl-D-aspartate (NMDA)-receptor-mediated effects, point to a functional NMDA antagonism by flupirtine. No binding of this drug at any known receptor has yet been demonstrated, but there are hints about a possible mechanism of action. Flupirtine maleate (hereafter referred to as flupirtine) was synthesized by Homburg, Degussa Pharma Group of Frankfurt, Germany in 1981 (1) and is available in Europe under the trademark of Katadolon ® (ASTA Medica AG, Frankfurt, Germany). Flupirtine can be described as a pyridine derivative that is substituted in the 2-, 3and 6-positions with different amino groups, (2-amino-3-ethoxy-carbonylamino-6-4-fluoro-benzylamino-pyridine maleate). It was originally selected for clinical evaluation as the most active compound in a group of analgesic amino-substituted pyridine derivatives. The molecular structure of flupirtine (Fig. 1) does not resemble that of any analgesic currently on the market. Its synthesis is a four-step process starting from 2,6-dichloro-3-nitro-pyridine (4). CNS Drug Reviews Vol. 4, No. 2, pp. 149–164 © 1998 Neva Press, Branford, Connecticut