Studies of the Metabolism of the Antimalarial Agent Primaquine

Primaquine revisited six decades after its discovery

“…MAQ is not very active in inducing MetHb formation, thus shows lower toxicity indices as compared to other PQ metabolites [148,152,153]. However, an early report of Bolchoz et al described that, when MAQ was incubated with rat and human liver microsomes, a single metabolite of MAQ was detected and identified as 6-methoxy-8-(Nhydroxy)aminoquinoline (MAQ-NOH, 19).…”

“…Finally, formation of N 8 -hydroxyprimaquine (14) metabolite has also been proposed, but comparison of the metabolite alleged to be 14 with synthetic N 8 -hydroxyprimaquine failed to confirm the hypothesis [153].…”

“…The most representative hydroxylated metabolite is 5-hydroxyprimaquine (5-HPQ, 8) [146][147][148][149][150][151][152][153]. According to Bowman et al [146], this metabolite induced methemoglobin formation and depletion of glutathione (GSH), when incubated with suspensions of rat erythrocytes.…”

“…6-Methoxy-8-aminoquinoline (MAQ, 18) is thoroughly referenced in works devoted to PQ metabolism [148,[151][152][153][154][155]. MAQ is not very active in inducing MetHb formation, thus shows lower toxicity indices as compared to other PQ metabolites [148,152,153].…”

Photooxidation products of primaquine Structure, antimalarial activity and hemolytic effects

“…N-acylated primaquines are also inactive tissue schizontocides in vitro which supports the view that the terminal amino group in the side chain of primaquine may be necessary for antimalarial activity [5]. Further elucidation of antimalarial and possibly associated hemolytic effects present in oxidation products of primaquine [6] suggested a study of several compounds obtained from 1 and its N-acylated analogs by photochemical oxidation. This included a blue dye for which Strother et al [6] proposed the tricyclic quinonimine structure 2, now revised to that of oquinone 4, readily obtained from 5-hydroxydemethylprimaquine (5) as described here.…”