Search

Phenylethanolamine, p-octopamine and m-octopamine contents were determined in the hypothalamus and the brain stem of spontaneously hypertensive Rats (S.H.R. Kyto) and the corresponding controls (Wistar Kyoto). In three-week-old Rats, phenylethanolamine and p-octopamine are found to be present in S.H.R. hypothalamus and brain stem at concentrations twice as high as compared to Wistar Kyoto Rats. The amount of m-octopamine is 5-fold higher in the brain stem of S.H.R. Rats as compared to Wistar Kyoto Rats.

After i.v. administration of DL-norephedrine 14C to the rat (535 mug/kg), approximately 75% of the radioactivity was eliminated during the first 18 hr in the urine. Beside the unchanged drug (71.5% of the total urinary radioactivity), the main metabolite was alpha-methyloctopamine (18%), a parahydroxylated derivative of which 68% were excreted as glucuronide conjugates. Kinetic studies of DL-norephedrine in different organs showed that the affinity of tissues for the amine did not change with time. Captation was important and rapid in lungs, adrenals, spleen and heart. The brain was marked by a slow increase of drug level during the first 2 hr. However, the terminal semi-exponential kinetic slopes of DL-norephedrine concentration showed that the elimination processes of the drug were the same in each tissue. The affinity of tissues for alpha-methyloctopamine was shown to be much more specific; its uptake was higher in organs which are rich in adrenergic nerve endings (heart, adrenals and spleen). These results confirm the role of this hydroxylated amine as a false neurotransmitter. A whole body autoradiography in the mouse showed an important uptake of DL-norephedrine 14C in salivary glands and periocular structures.

We have attempted to trace the development of the concept which stresses that the encephalopathy often seen with hepatic failure may be the result of derangement in amino acid metabolism in patients with failing livers. We have also proposed that the infusion of solutions which may normalize these plasma amino acids and decrease the amount of toxic aromatic amino acids within the circulation may help in the amelioration of the symptoms of hepatic encephalopathy. We believe that in our studies to date, the use of this solution has been a significant advantage in the care of these extremely ill patients. We would hope that when the solution becomes generally available, the provision of such solutions to such patients will result in the salvage of some lives lost at the present time because of hepatic failure and encephalopathy.