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

Abstract

The effects of the non-peptide vasopressin V 2 receptor antagonist, 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1 H-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 Na + 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 V 2 receptors. These observations might suggest a new, effective approach to the treatment of subarachnoid haemorrhage-induced cerebral oedema in humans.