DISTRIBUTION OF INHIBITORS IN ANIMALS 



397 



time. The changing is due mainly to the drop in plasma mercurial and the 

 minor increase in tissue mercurial from 2 to 24 hr is certainly not indicative 

 of a rising concentration of free mercurial. The data do show that renal 

 tissue does accumulate mercurial well; if this is due to exposure to a higher 

 concentration than for other tissues, it may be indicative of a higher initial 

 free concentration and relatively greater enzymic inhibition. 



A more detailed pattern of inhibitor distribution has been established 

 within the central nervous system for the amine oxidase inhibitor, isoniazid 

 (Barlow, et al., 1957), and the carbonic anhydrase inhibitor, acetazolamide 

 (Roth, et al, 1959). The results in Table 8-2 show that the distributions for 

 these two inhibitors are far from uniform and Fig. 8-1 demonstrates the 

 changes in distribution with time for acetazolamide. Autoradiograms of 

 brain sections also clearly showed the unequal patterns of distribution. 

 Thus even within a single type of tissue, an inhibitor may enter certain cells 

 at a greater rate, and it is likely that, if smaller region could be analyzed, 



Fig. 8-1. Concentrations of acetazolamide (Diamox) in various regions of the cat 

 brain following intravenous injection of 1.50 mg/kg. R is the ratio of the concen- 

 tration in the region specified to the concentration in the spinal cord. (From Roth 

 et al., 1959.) Curve 1: hypothalamus; curve 2: hippocampus; curve 3: caudate nu- 

 cleus (ventral surface); curve 4: cerebral white matter (ventral surface); curve 5: 

 cortex; curve 6: thalamus; curve 7: globus pallidus; curve 8: medulla (centrum); 

 curve 9: cerebrospinal fluid. 



