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Plasma levels, elimination and metabolic fate of 4a-amino-8-chloro-2-methyl-1,2,3,4,4a,10a-hexahydro-10H-benzopyrano[3,2-c]pyridin-10-ylacetic acid lactam, a new antidepressive agent, in rats and dogs.

After single intravenous administration to dogs, 4a-amino-8-chloro-2-methyl-1,2,3,4,4a,10a-hexahydro-10H-benzopyrano[3,2-c]pyridin-10-ylacetic acid lactam (LM 1404) was rapidly distributed. Elimination from plasma was biphasic and dose-independent between 1 and 10 mg/kg, with a half-life for the beta-phase of 4.5 hr. After oral administration, LM 1404 was quickly and nearly completely absorbed. In rats, LM 1404 was rapidly absorbed and eliminated from plasma with a terminal half-life of 2.5 hr. The N-demethylated metabolite (LM 1580), which has a pharmacological activity nearly identical to that of LM 1404, was very abundant in plasma of both species, with half-lives of 13 hr in dogs and 3.5 hr in rats and areas under the curves respectively 2 and 4 times that of LM 1404. Urinary excretion was extensive; unchanged drug amounted to 7 and 1.5% and LM 1580 to 70% in dogs and rats.