AN ONTOGENETIC STUDY OF PHENOBARBITAL-C¹⁴ IN CAT BRAIN

¹ Department of Pharmacology and the Division of Neurology, Department of Medicine, The University of Chicago, Chicago, Illinois

1. An ontogenetic study of penetration and distribution of phenobarbital-C¹⁴ in the brain and cerebrospinal fluid of cats is reported.

2. No metabolites of phenobarbital were found in the brain and spinal fluid of adult cats and newborn kittens.

3. At early time periods a distinctly nonuniform distribution of phenobarbital in cat brain is evident. We have demonstrated that white matter was less easily penetrated than gray in the adult cat and this is presumed to be due in part to the laminated nature of tile myelin sheath. The eventual distribution of phenobarbital in brain regions is nearly equal. No one area of gray matter, through to 6 hours, showed an unusual local accumulation of the drug.

4. Phenobarbital in the newborn kitten disclosed a reverse distribution pattern from that of the adult cat in relation to white matter and cortex. The distribution in white matter was shown to have an inverse relationship to myelin development.

5. Evidence is presented which indicates that phenobarbital concentration in cerebrospinal fluid is comparable to an ultrafiltrate of plasma, and it is suggested that an appreciable fraction of brain phenobarbital is bound.

6. The variations in distribution with time and area of brain emphasize the need to analyze multiple areas as a function of time. Autoradiography is a valuable tool in such studies.