EFFECTS OF NIRAVOLINE (RU-51599), A SELECTIVE KAPPA-OPIOID RECEPTOR AGONIST ON INTRACRANIAL-PRESSURE IN GRADUALLY EXPANDING EXTRADURAL MASSLESION

It has recently been reported that kappa-opioid receptor agonists inhi bit antidiuretic hormone secretion and promote water excretion in huma ns and animals. We investigated the effect of niravoline (RU 51599), a selective kappa-opioid receptor agonist in the treatment of intracran ial hypertension. Acute intracranial hypertension was induced in cats by continuous inflation of an extradural balloon with physiological sa line at the constant rate of 0.5 ml/h for 3 h. At this point, inflatio n was discontinued and the balloon remained expanded for an additional hour after which it was deflated. In the post-deflation period, monit oring continued for 1 h. The control group (n = 8) received ringer's l actate solution only, while the treatment group (n = 8) received an in travenous (IV) injection of 1.0 mg/kg of niravoline, every hour at the beginning of balloon inflation, during balloon inflation, in post-inf lation, and at deflation time (5 doses). Changes in intracranial press ure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pres sure (CPP), electroencephalogram (EEG), blood gases, pupil size, serum electrolytes, and osmolality were measured in both groups. Brain wate r content was determined in a separate group of eats at the end of a 3 -h extradural brain compression. Compared to the untreated group, the niravoline-treated group had a significantly lower ICP and higher CPP at the 2 and 3 h during balloon inflation, in post-inflation, and in p ost-deflation periods. Brain water content was significantly reduced i n niravoline-treated animals. No significant change was observed in se rum osmolality throughout the experiment. Our results indicate that th e mechanism by which niravoline reduces ICP is partly via a reduction in brain water content. Also, the current findings suggest that in cli nical situations in which ICP is elevated due to the pressure of an ex tradural mass, niravoline may effectively reduce ICP while maintaining adequate CPP until the mass is removed.