Facilitation of Leão's spreading depression by a pyrrolopyrimidine derivative

Abstract

The facilitatory effect of the drug BW 58-271 (2-methyl 4-benzyl-aminopyrrolo/2,3-d/pyrimidine) on Leão's spreading depression was examined in 67 adult rats, anaesthetized with Allobarbital or Nembutal. Intraperitoneal injection of BW 58-271 (10 mg kg ) increased the cortical spreading depression susceptibility, increased the amplitude of the slow potential change by 60% and the propagation rate by 28%. The drug abruptly increased the percentage of cortical spreading depression waves penetrating into the caudate nucleus from 34% to 100% and reduced the cortico-caudate or caudato-cortical conduction time from 5.6 to 3.1 min. All these effects were maximal 20 min after BW 58-271 injection and decayed over the following 2 hr. Measurements with potassium selective microelectrodes showed that BW 58-271 did not change the resting level of extracellular potassium in the cortex but increased the peak extracellular potassium level attained during spreading depression from 65 to 85 mm Reverberation of cortical spreading depression around a circular lesion (5.2 mm in diameter) in the frontal cortex was enhanced by BW 58-271; the number of completed cycles increasing from 12 in control to 53 in treated rats. The changes of the spreading depression properties indicate that the drug increases potassium permeability of the neural membrance without interfering with the mechanism of the active transport.