Figure 3

Effect of oral flupirtine and placebo on the recovery cycle of electrical excitability in motoneurones to abductor pollicis brevis in healthy subjects. Stimulus–response curves were obtained using unconditioned test stimuli of 1 ms duration. These established the maximal CMAP to supramaximal nerve stimulation and the size of the submaximal target CMAP (~ 40% of maximum). The stimulus current necessary to produce the target potential using a 1 ms test stimulus is referred to as the “threshold” for that potential. Electrical excitability, i.e. the current required to maintain a 40% compound muscle potential response, was determined at discrete interstimulus intervals following a supra-maximal stimulus (A). The representative example in panel B illustrates the changes in the recovery cycle observed after oral uptake of flupirtine (200 mg) or placebo compared to baseline measures. Changes in the recovery cycle of motor axons were quantified with the empirically determined values of refractoriness at 2 ms (D) and 2.5 ms (E) and excitability at 5 ms (F) and 7 ms (G). The relative refractory period (C) was determined respectively by linear interpolation and first-order exponential fits (see Methods). RRP in motoaxons to APB (C) was reduced 2 hours after oral flupirtine (3.40 ± 0.07 ms; p < 0.01) but not placebo (3.45 ± 0.12 ms, p = 0.53). Oral flupirtine also reduced refractoriness at 2 ms and 2.5 ms (D, E). In contrast to the effect of flupirtine in vitro, the magnitude of superexcitability at both 5 and 7 ms determined in vivo was not affected by flupirtine (F,G)