Peters W, Robinson B L
Ann Trop Med Parasitol. 1984 Dec;78(6):561-5.
Two new Mannich base antimalarials, WR 194,965 and 228,258 exhibit blood schizontocidal action against Plasmodium berghei in vivo. This action is retained also against the P. berghei NS line which has a low level of resistance to chloroquine. While WR 228,258 is also active against the highly chloroquine-resistant RC line, WR 194,965 is not. Both compounds show slightly reduced activity against the highly mefloquine-resistant N/1100 line. WR 225,448, an 8-aminoquinoline, is as active against blood stages of the NS, RC and N/1100 lines of P. berghei as against the N strain, and more so on a dose/weight basis than the first two compounds. It shows a low level of cross-resistance against the primaquine-resistant P line. WR 225,448 has a clear causal prophylactic effect on the pre-erythrocytic schizonts of P. yoelii nigeriensis. While WR 194,965 and 228,258 also appeared to act on these stages, the effect is most probably due to residual action on emerging erythrocytic merozoites since pre-erythrocytic schizonts in treated animals were morphologically indistinguishable from those of the untreated control.
两种新型曼尼希碱抗疟药WR 194,965和228,258在体内对伯氏疟原虫具有血内裂殖体杀灭作用。这种作用对氯喹低水平耐药的伯氏疟原虫NS株同样有效。虽然WR 228,258对高度耐氯喹的RC株也有活性，但WR 194,965则没有。两种化合物对高度耐甲氟喹的N/1100株的活性略有降低。8-氨基喹啉WR 225,448对伯氏疟原虫NS、RC和N/1100株血内期的活性与对N株的活性相同，且按剂量/体重计算比前两种化合物更强。它对耐伯氨喹的P株显示出低水平的交叉耐药性。WR 225,448对约氏疟原虫尼日尔株的前红细胞期裂殖体有明显的病因性预防作用。虽然WR 194,965和228,258似乎也作用于这些阶段，但这种作用很可能是由于对新出现的红细胞内裂殖子的残留作用，因为经治疗动物的前红细胞期裂殖体在形态上与未治疗对照的裂殖体无法区分。
