EVALUATION OF THE ABILITY OF IRBESARTAN TO CROSS THE BLOOD-BRAIN-BARRIER FOLLOWING ACUTE INTRAGASTRIC TREATMENT

The present study evaluated in functional tests the ability of the ang iotensin AT(1) receptor antagonist irbesartan, ]-4-yl)methyl]-1,3-diaz a-spiro[4,4]non-1-en-4-one, in comparison to losartan, 2-n-butyl-4-chl oro-5-hydroxymethyl-1-[(2'(1 H-tetrazol-5-yl) bi-phenyl-4-yl)methyl]im idazole, to cross the blood-brain barrier following acute intragastric administration. Two tests were used: the dipsogenic response to intra cerebroventricular injection of angiotensin II, and Nai intake in resp onse to adrenalectomy. In normotensive rats, irbesartan reduced the di psogenic response to angiotensin II, 10 pmol per rat, at the dose of 9 0 mg/kg, but not at lower doses. Losartan significantly reduced angiot ensin II-induced drinking at 30 mg/kg, but not at a lower dose. In spo ntaneously hypertensive rats, irbesartan reduced the response to angio tensin II at 50 mg/kg, but not at lower doses, while losartan signific antly inhibited angiotensin II-induced drinking even at 10 mg/kg. In a drenalectomized rats, the intake of 2% NaCl was inhibited by the intra gastric administration of losartan 30 or 50 mg/kg, while irbesartan di d not reduce it in doses up to 50 mg/kg. The results of the present st udy consistently indicate that after acute intragastric administration , the ability of irbesartan to cross the blood-brain barrier is lower than that of losartan. (C) 1998 Elsevier Science B.V. All rights reser ved.