Sabeluzole administration does not enhance fast axonal transport in normal adult rat sciatic nerve

Sabeluzole (R58735, Janssen Research Foundation) increased rates of axonal transport in short term tissue culture experiments and in rats with streptozotocin-induced diabetes. The drug was tested for its subacute (3 days) net effect on axonally transported substances in motor, sensory, and adrenergic axons of normal adult rats. Sabeluzol was given once daily for 3 days, 1 or 10 mg/kg/day intraperitoneally. Immunofluorescence was used to identify transported material. Three or 6 hr after crushing the sciatic nerves, to interrupt anterograde and retrograde intraaxonal transport, cytofluorimetric scanning was used to quantitate accumulated immunoreactive material. Compared with vehicle treated control rats, no clear differences in the net amounts of accumulated material, or in rates of accumulation, were detected in any axonal type. Since the short-term crush procedure interrupts ongoing axonal transport, the accumulation pattern reflects the transport characteristics in the crushed axons. The absence of clear increases in transport of several substances in this study indicates that sabeluzole did not enhance net axonal transport above control levels in peripheral axons of normal adult rats. Possible reasons for the discrepancy with earlier observations on the effect of sabeluzole on fast axonal transport is discussed.