Action of 4-aminopyridine on the cerebral circulation

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Abstract
4-Aminopyridine (4-AP) facilitates inhibitory and excitatory synaptic activity in the CNS, and may be a drug of potential therapeutic use in brain diseases with a disturbed synaptic transmission. The vasomotor effects upon isolated feline brain vessels, and regional cerebral blood flow and brain cortical metabolism in rats were examined. At high concentrations (.apprx. 106 M) a minor vasoconstriction was obtained of isolated pial vessels. Measurements of regional cerebral blood flow using the 14C-ethanol technique resulted in a significant increase in blood flow of caudate nucleus (93%), thalamus (74%) and cerebellum (82%). The arteriovenous O2 difference of cortical tissue was reduced from 3.20 mmol O2/ml to 1.69 mmol O2/ml by 4-AP. This was not associated with an increase in cortical blood flow. Calculation of the cortical metabolic rate of O2 failed to demonstrate any significant change.