PHARMACOKINETICS DO NOT EXPLAIN THE ABSENCE OF AN ANESTHETIC EFFECT OF PERFLUOROPROPANE OR PERFLUOROPENTANE

In conflict with the prediction of the Meyer-Overton hypothesis, perfl uoropropane (C3F8) and perfluoropentane (C5F12) have no anesthetic eff ect in rats. To test whether this resulted from a failure of the inspi red drugs to reach the brain, we determined the increase in partial pr essures of C3F8 and C5F12 in the blood and brains of rats exposed to 0 .65 ata of each drug. C3F8 and C5F12 blood/gas partition coefficients equaled 0.00125 +/- 0.00037 (mean +/- SD, n = 9) and 0.00277 +/- 0.000 82 (n = 4), and brain/gas partition coefficients equaled 0.0119 +/- 0. 0002 (n = 4) and 0.0229 +/- 0.0055 (n = 7), respectively. As a fractio n of the inspired value (Pa/PI), the partial pressures of C3F8 and C5F 12 in blood (Pa) were 0.99 +/- 0.12 and 0.69 +/- 0.19, respectively, 3 0 min after administration. The increases in cerebral (Pb) partial pre ssures of both drugs paralleled the arterial increases (Pb/PI = 0.85 /- 0.02, and 1.05 +/- 0.03, respectively at 30 min), with C3F8 reachin g a plateau at 2 h of 96% +/- 4% of the partial pressure of inspired g as. We conclude that failure of C3F8 and C5F12 to reach the brain does not account for the absence of an anesthetic effect of these compound s.