Neural pharmacokinetics of epinephrine

Abstract

The effects of 3H-epinephrine on the duration of block and on the time course of uptake and efflux of local anesthetic (14C-lidocaine hydrochloride) were determined in the infraorbital nerve of the pentobarbital-obtunded rat. Epinephrine, 1:50,000, doubled the duration of behavioral block produced by 37 mM (1 per cent) lidocaine; 1:100,000, 1:200,000, and 1:400,000 prolonged the block correspondingly less, the relation being inversely proportional to the log of the epinephrine concentration. The neural level of 3H-epinephrine reached a peak within 10 minutes and then declined linearly with time, as did the associated neural level of 14C-lidocaine. Linearity apparently results from the summation of the time-linked decreasing diffusion gradient of drug and the consequently increasing rate of perfusion with blood. Phentolamine antagonizes the epinephrine-caused prolongation of behavioral block. The results suggest that in spinal anesthesia the extent of dilution of an epinephrine additive by cerebrospinal fluid will significantly affect the duration of the block.