Disposition and metabolism of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine in rats, dogs, and monkeys.
The disposition and metabolism of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a new agent with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties, was studied in rats, dogs, and rhesus monkeys. [3H]benzene-MK-801 was administered orally at a dose of 1 mg/kg. MK-801 was measured in plasma by GLC using a nitrogen detector; the overall sensitivity of the method was 3 ng/ml. Radioactivity was excreted mainly in urine of dogs and monkeys but fecal excretion in rats was also extensive. The apparent plasma t1/2 of MK-801 in the rat and dog was approximately 1 hr. Maximal plasma levels of MK-801 in the rat, dog, and monkey were 46 (0.5 hr), 16 (0.25 hr), and 10 (2 hr) ng/ml, respectively. Radioactivity was extensively excreted in rat bile and was widely distributed among various tissues. Major metabolites of the drug in rat and dog urine were the 2- and 8-hydroxy analogs (rat) and the N-hydroxy derivative (dog).
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism; D000927:Anticonvulsants / Q000378:metabolism*; D003986:Dibenzocycloheptenes / Q000378:metabolism* / Q000652:urine; D016291:Dizocilpine Maleate; D004285:Dogs; D005243:Feces / Q000032:analysis; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013566:Sympathomimetics / Q000378:metabolism*; D014018:Tissue Distribution
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D013566:Sympathomimetics; D016291:Dizocilpine Maleate