Comparison of the biological effects in rat of high doses of two 4-amino-7-chloroquinoline derivatives: chloroquine and glafenine.

When given orally in elevated but nonlethal doses (150 to 450 mg/kg, on 2 consecutive days), glafenine induces in rats (body weight 100 g) a transient nephritis with an increase in blood urea, hypertrophy of adrenals, and some changes in the serum proteinogram. These effects do not appear to be due to the 4-amino-7-chloroquinoline structure from which glafenine is derived, as they are not observed with the structural analogue chloroquine given at equimolar doses under the same conditions. Further, they do not appear to be due to glycerol, the by-product of metabolic glafenine hydrolysis. The responsible molecule appears to be either glafenine itself or its acid metabolite 4-(0-carboxyphenylamino) 7-chloroquinoline.