title: Niravoline, a selective kappa-opioid receptor agonist effectively reduces elevated intracranial pressure.
abstract: To ascertain the effects of niravoline (RU 51599, a selective kappa-opioid receptor agonist) on elevated intracranial pressure with mass lesion, the authors experimentally induced intracranial hypertension in cats by progressive inflation of an extradural balloon with physiological saline at the constant rate of 0.5 ml/h for 2.5 h. After 2.5 h, inflation was discontinued, but the balloon remained inflated for an additional 3 h. Immediately after cessation of balloon inflation and while the balloon remained expanded, the control group (n = 8) received ringer's lactate solution only. In the treatment group (n = 8), each cat was treated with an intravenous administration of niravoline at a dose of 1.0 mg/kg immediately after the cessation of balloon inflation and every hour for 3 h in post-inflation period (three injections total). Changes in intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), electroencephalogram (EEG), pupil size, blood gasses and pH, plasma osmolality and electrolytes, and brain water content were studied in both groups. Compared with the untreated group, niravoline treatment produced significant decreases in ICP and significant increases in CPP at 1, 2, and 3 h post-inflation in the presence of an extradural mass lesion. Brain water content was significantly reduced both in the compressed and contralateral hemispheres following niravoline treatment. No significant changes were observed in plasma osmolality and systemic arterial blood pressure following niravoline administration. The results from this present study provide further evidence that niravoline is effective in reducing elevated intracranial pressure, brain water content, and maintaining an adequate cerebral perfusion pressure even in the presence of an extradural mass lesion. Niravoline may offer a new therapeutic modality in head-injury patients with an acute intracranial, expanding mass lesion by providing a safer extended time-period until the mass can be surgically evacuated.
authors.affiliation: Department of Neurological Surgery, Kagawa Medical University, Kita-Gun, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nagao
authors.forename: I
authors.initials: I
authors.lastname: Bemana
authors.forename: H
authors.initials: H
authors.lastname: Kuratani
authors.forename: E
authors.initials: E
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D044482:Benzeneacetamides; D001794:Blood Pressure; D002404:Catheterization; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D004573:Electrolytes / Q000097:blood; D005260:Female; D007839:Functional Laterality; D019586:Intracranial Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007427:Intracranial Pressure / Q000187:drug effects*; D008297:Male; D011680:Pupil / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists*
chemical_list: D044482:Benzeneacetamides; D004573:Electrolytes; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C100946:niravoline