Effects of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine on the blood-brain barrier permeability in the rat

Histamine plays a role in the regulation of the blood-brain barrier functio n. In this study, effects of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanam ine (DPPE), an intracellular histamine binding site antagonist on the cereb rovascular permeability were investigated in control and post-ischemic male Wistar rats. Intravenous administration of DPPE, in a dose of 1 and 5 mg/k g, was not followed by any major clinical change, but 20 mg/kg proved to be toxic. A significantly (P < 0.05) increased permeability for sodium fluore scein (MW = 376) was seen in hippocampus, striatum, and cerebellum, but not in parietal cortex, of rats 2 h after the injection of 5 mg/kg DPPE, where as no increase was measured later. There was a more intense (5- to 12-fold) and prolonged elevation in Evan's blue-labeled albumin (MW = 67,000) extra vasation 2, 4, and 8 h after 5 mg/kg DPPE administration in each brain regi on. In parietal cortex, a dose-dependent increase in albumin extravasation developed 4 h after intravenous injection of 1, 5, and 20 mg/kg DPPE, but d oses applied resulted in no significant change in sodium fluorescein permea bility. Cerebral ischemia-reperfusion evoked by four-vessel occlusion cause d a significant (P < 0.05) increase in the permeability for albumin in each region, but few changes in that of sodium fluorescein. DPPE treatment fail ed to prevent the ischemia-reperfusion-induced changes in the blood-brain b arrier permeability. In conclusion, DPPE induced an increased permeability in the rat, which supports a role for histamine, as an intracellular messen ger, in the regulation of the blood-brain barrier characteristics. (C) 2000 Elsevier Science B.V. All rights reserved.