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  • Title: Relationship of guanabenz concentrations in brain and plasma to antihypertensive effect in the spontaneously hypertensive rat.
    Author: Meacham RH, Ruelius HW, Kick CJ, Peters JR, Kocmund SM, Sisenwine SF, Wendt RL.
    Journal: J Pharmacol Exp Ther; 1980 Sep; 214(3):594-8. PubMed ID: 7400962.
    Abstract:
    The antihypertensive agent guanabenz (E-2,6-dichlorobenzylidene aminoguanidine acetate. Wy-8678) was administered i.v. in single doses of 10, 32 and 100 microgram/kg to groups of spontaneously hypertensive rats. Mean arterial blood pressure and heart rate were monitored continuously. Animals were decapitated at predetermined time intervals and concentrations of the drug in whole brain and plasma were measured by a specific gas chromatographic method. After an initial transient increase in blood pressure, significant dose-dependent maximal decreases in pressure of 15 +/- 8, 46 +/- 20 and 59 +/- 15 mm Hg (mean +/- S.D.) were observed 15 to 30 min after injection of the above respective doses. At the line of the maximal decreases in pressure (T delta max), concentrations of guanabenz in brain were 10 +/- 2, 29 +/- 8 and 89 +/- 21 ng/g and correlated significantly with dose and the magnitude of blood pressure change. The correlation between concentration in brain and change in blood pressure was also significant at subsequent sacrifice times. Concentrations of guanabenz in plasma were below the limit of detection after the 10 microgram/kg dose. At the two higher doses, concentrations in plasma were dose related but did not correlate with decreases in blood pressure. The correlation between concentration in brain and change in blood pressure is in agreement with the predominantly central mechanism of action of guanabenz.
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