Mefenidil (5-methyl-2-phenyl-4-imidazole-acetonitrile) has been reported to be a selective cerebral
vasodilator. We examined the specificity of this
vasodilator by using the radiolabeled
microsphere technique to compare changes in cerebral blood flow (CBF) with those in other organs. Measurements were made in
pentobarbital-anesthetized dogs
at 10 min of continuous i.v. infusion of
mefenidil at rates of 0.025, 0.25 and 2.5 mg/min/kg. Systemic vascular resistance decreased at 0.25 mg/min/kg without a change in CBF. At the highest infusion rate, CBF increased by 54 +/- 15% (+/- S.E.; n = 9) accompanied by a 9-mm Hg rise in intracranial pressure and a 14-mm Hg fall in mean aortic pressure. However, cardiac output increased by 68 +/- 8%, which was distributed primarily to right ventricle (541 +/- 95%), left ventricle (488 +/- 109%), small intestine (136 +/- 31%) and large intestine (57 +/- 15%). Within the brain, thalamic and brainstem regions had larger increases in blood flow than cerebellum and cerebrum. Caudate nucleus had a greater percentage of response than white matter. Using the cerebral venous outflow technique in another series of seven dogs,
mefenidil (40-mg/kg i.v. bolus) produced a 20 +/- 8% increase in CBF with no change in O2 uptake. These data show that
mefenidil is capable of increasing CBF in healthy brain without stimulating O2 uptake. However, the clinical usefulness of
mefenidil as a cerebral
vasodilator may be limited by the accompanying arterial
hypotension due to systemic vasodilation, which was most prominent in heart and gut.