Metabolism of 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline, a phenylethanolamine N-methyltransferase inhibitor. I. Disposition following administration to the rat and dog

1. Following oral dosing of 7,8-dichloro-1,2,3,4-tetrahydro[1-14C]isoquinoline (14C-DCTQ) to rats, the plasma 14C increased steadily for 24h. In dogs, the 14C peak occurred at 40min. The concn. of unchanged drug in rats remained constant for 2h following oral administration then decreased with a t1/2 of 18h. In the dog unchanged drug levels were highest at 20min then fell with a t1/2 of 1·2h.2. Intravenous administration of 14C-DCTQ to rats resulted in a biphasic fall in plasma unchanged drug levels with t1/2 of 1.5 and 18h. In the dog after intravenous administration, plasma levels of unchanged drug fell with t1/2 of 1·2h.3. Binding of the drug to plasma protein in vitro was 97.9% in rat, 99.4% in dog 99.7% in human. Distribution in blood was 39.5% cellular, 59.2% protein, 1.3% free, in rat; 13.4% cellular, 86.1% protein, 0.5% free, in dog; and 7.5% cellular, 92.2% protein and 0.3% free, in human.4. Tissues in rat that had higher concn. of 14C than blood, in decreasing order were: kidney, liver, adrenal,...