Summary
Intravenous injection of the antihypertensive agent R28935 and its pharmacologically less active threo-isomer R29814 resulted in a distribution profile in the cat brain which differed from the regional localization after administration via the left vertebral artery. Although the two isomers had the same physicochemical properties, R28935 penetrated more readily into the CNS.
Intravenous administration resulted in almost equal levels in all brain parts, whereas after injection into the vertebral artery caudal structures contained more of both compounds than rostral structures. Differences existed between the concentrations in homotopic brain areas, especially in the brain stem.
From comparison of the levels of R28935 after injection of an equiactive dose either i.v. or into the vertebral artery it is tempting to speculate that the mesencephalic tegmentum, the nucleus of the solitary tract, the inferior colliculi and/or the locus coeruleus are possible sites of the hypotensive action.
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Loonen, A.J.M., Soudijn, W., van Rooij, H.H. et al. The regional localization of R28935 in the cat brain as dependent on the route of administration. Naunyn-Schmiedeberg's Arch. Pharmacol. 309, 281–285 (1979). https://doi.org/10.1007/BF00504761
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DOI: https://doi.org/10.1007/BF00504761