The effects of
p-chlorophenylalanine, an inhibitor of
serotonin synthesis,
indomethacin, an inhibitor of
prostaglandin synthesis,
cyproheptadine, a
serotonin,
bradykinin and
histamine antagonist, were assessed separately and in combination with
chloroquine (CQ) in Vom strains of Swiss albino mice (18-22 g) of either sex infected intraperitoneally with 1 x 10(7) Plasmodium yoelii nigeriensis-induced
malaria. As prophylactic, these agents reduced from 31.9 +/- 4.5 to 16.1 +/- 8.1% the level of
parasitemia relative to control but had no appreciable activity as curative agents when administered subcutaneously once daily for 4 days after 72 h of parasites innoculum in vivo. However, CQ alone and the combination of these agents with CQ in curative and prophylactic treatments significantly reduced (from 50.3 +/- 5.8 to 4.9 +/- 0.75%) the level of
parasitemia (P < 0.05), which was taken only once 72 h after the parasites innoculum. The prophylactic result was shown to produce better results than the curative treatment. The data indicate that inhibitors and an antagonist can reduce the
parasitemia load (the extent of damage and the severity of
infection) as well as enhance the effects of CQ when combined with it for
malaria therapy. The study reveals that the production of
autacoids in established
infection renders
autacoid inhibitors and an antagonist ineffective for radical cure in malarial mice; however, selective inhibition of local
hormones implicated in the pathological manifestations of
malaria infection by
autacoid inhibitors and an antagonist may be a possible pathway to reduce the severity of
infection and the associated tissue damage and to enhance the efficacy of available
anti-malarials.