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-1 H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by subarachnoid haemorrhage were studied in rats. Subarachnoid haemorrhage induced signi...

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Bibliographic Details
Published in:European journal of pharmacology 1999-01, Vol.364 (2), p.115-122
Main Authors: László, Ferenc A., Varga, Csaba, Nakamura, Shigeki
Format: Article
Language:English
Subjects:
Animals
Antidiuretic Hormone Receptor Antagonists
Benzazepines - pharmacology
Biological and medical sciences
Body Water - drug effects
Brain - drug effects
Brain - metabolism
Brain - physiopathology
Brain Edema - physiopathology
Brain Edema - prevention & control
Cerebral oedema
Diuresis - drug effects
Dose-Response Relationship, Drug
Drinking - drug effects
Male
Medical sciences
Miscellaneous
Neuropharmacology
Non-peptide
Osmolar Concentration
Pharmacology. Drug treatments
Potassium - metabolism
Rats
Rats, Wistar
Sodium - metabolism
Subarachnoid haemorrhage
Subarachnoid Hemorrhage - physiopathology
Urination - drug effects
Urine
Vasopressin receptor antagonist
Vasopressins - blood
Vasopressins - drug effects
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Summary: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.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(98)00836-X