Mefenidil (McN-2378), a selective cerebral vasodilator, was shown to increase CBF in healthy brains without stimulating O2 uptake in a dog anesthesia model.

Mefenidil (0.025, 0.25, and 2.5 mg/min/kg; i.v. infusion for 10 min; dogs) decreased systemic vascular resistance 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, the thalamic and brainstem regions had larger increases in blood flow than the cerebellum and cerebrum. The 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 brains 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 the heart and gut.[1]