THE PHYSIOLOGICAL DISPOSITION OF H³-DICHLOROISOPROTERENOL

¹ Department of Pharmacology, Division of Basic Health Sciences, Emory University, Atlanta, Georgia

The fate of dichloroisoproterenol (DCI), labelled with H³ on the position, has been investigated in dogs and mice using intravenous doses of 7 to 10 mg/kg. In the dog, DCI rapidly disappeared from plasma (half-life of 1.4 minutes), but this phase was followed by two others with progressively slower rates of disappearance. The rapid initial disappearance of the drug from plasma was associated with extensive localization in most tissues, especially the lung. High concentrations of DCI were also found in various parts of the dog brain, which is in contrast to what has been reported for the catecholamines. Furthermore, tissue localization was associated with a long duration of action, which again distinguishes this blocking drug from the action of the catecholamines. Rapid metabolism of DCI was demonstrated by the finding that less than half of the radioactivity found in plasma 20 minutes after administration was due to the drug. The metabolites were present in large amounts in urine, but not in tissues, and were identified as 3,4-dichloromandelic acid and the glucosiduronate and probably sulfate conjugates of DCI.

The mouse, in contrast to the dog, was shown to metabolize DCI by removing H³ from the position of the molecule. Evidence was the loss of radioactivity from the whole mouse and the large fraction of H³ which was found in the water of the animals.