The mechanical responses of the gastrointestinal tract to anti malarial drug primethamine-sulphadoxine (fansidar) and /or activated charcoal (A/C) were investigated using isolated rat ileal smooth muscle. Fansidar (5.0x10-2 to 4.5x101 M) elicited concentration-dependent relaxation of the gut smooth muscle. ACh inhibited fansidar induced relaxation, while atropine potentiated action of fansidar. Although the mechanism of action of fansidar is not clear, it is plausible that the effect of fansidar might be direct on the smooth muscle or indirect via neurotransmitter release. The gut vascular smooth muscle exhibited two distinct modes of signaling in the presence of A/C and fansidar: incubation with drug followed by A/C (5 minutes later) significantly (p <0.05) reduced the relaxation responsiveness of the tissue as well as the concentration of the drug compared with the situation when activated charcoal was followed by drug. Fansidar concentration (EC50) before and after the application of activated charcoal was 2.0x100 M and 1.5x100 M; these elicited respectively, 59% and 41% relaxation of the smooth muscle. These studies show that fansidar relaxes gut smooth muscle, and immediate administration of activated charcoal after drug ingestion reduced the mechanical responsiveness of the smooth muscle to drug. These features may render activated charcoal a unique therapeutic agent in ameliorating the toxicological effects of drugs/poisons in the gastrointestinal tract. There was no detectable difference in the inherent rhythmic spontaneous activity of the ileal smooth muscle in the presence or absence of activated charcoal (2.5x10-4 to 1.25x10-2 M).
Key words: Anti- malarial drug fansidar, activated charcoal- dual signaling, relaxation smooth muscle, ileum.
(Global Journal of Pure and Applied Sciences: 2003 9(2): 229-234)