Vasopressin receptor antagonist OPC-31260 prevents cerebral oedema after subarachnoid haemorrhage

The effects of the non-peptide vasopressin V-2 receptor antagonist, 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by subarachnoid haemorrhage were studied in rats. Subarachnoid haemorrhage induced significant water retention after water loading, increased the brain content of water and Naf and increased plasma vasopressin levels. The water retention and brain water and Na+ accumulation were prevented by OPC-31260 administration, but the plasma vasopressin levels were further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of antidiuresis and disturbances in brain water and electrolyte balance in response to subarachnoid haemorrhage. The subarachnoid haemorrhage-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on renal tubular function: it blocks the renal vasopressin V2 receptors. These observations might suggest a new, effective approach to the treatment of subarachnoid haemorrhage-induced cerebral oedema in humans. (C) 1999 Elsevier Science B.V. All rights reserved.