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The metabolites of dl-3-n-butylphthalide(NBP), a novel drug with promising protective action against cerebral ischemia, was studied in rats. Two main in vitro metabolites of NBP, M I and M II, were isolated and purified from rat liver microsome incubating system by using HPLC. The structure elucidation was mainly accomplished by spectral studies(UV, 1H-NMR, MS). Within 24 h following i.g. 3H-NBP, the total radioactivity excreted in urine and feces was 73.7% of the dose. Comparing with previous study, within 72 h following i.g. NBP, the total prototype drug excreted in urine and feces was 2.53% of the dose. This result excludes the possibility that NBP accumulates in vivo. The urine and brain homogenate of the rats(i.g. 3H-NBP) were analyzed by TLC. M I and M II were found in urine and M I was found in brain only. Furthermore, the ratio of radioactive M I to proptype drug was 1:1 in rat brain within 1 h following i.g. 3H-NBP. So, M I and M II were supposed to be the two main in vivo metabolites of NBP and M I might be an active metabolite.

The antisecretion effect of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E) was studied in perfusing rats in vivo. The results showed that PG6E at the dose 0.1 mg.kg-1 decreased markedly the acid secretion and antagonized the gastric acid secretion induced by histamine, pilocarpin and pentagastrin in rats. This action of PG6E appeared to be similar to that of cimetidine (40 mg.kg-1).

The effects of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E), in experimental ulcers induced by absolute alcohol, HCl, indomethacin, pyloric ligation and chronic acetic acid in rats were studied. PG6E at doses 10-80 micrograms.kg-1 was shown to have significant protective effect. PG6E (30-60 micrograms.kg-1) was also found to reduce markedly the acid secretion, pepsin activity, DNA content of the juice collected from pylorus ligated stomach of rats and increase markedly the content of gastric mucosa hexosamine in mice given PG6E (30-60 micrograms.kg-1 po for 3 d). At doses of 40-80 micrograms.kg-1, PG6E was able to have no significant effect on gastric emptying time in rats and gastrointestinal tract movement in mice. It appears that PG6E was shown to inhibit the aggressive factors and increase the protective factors of gastric mucosa. This may hopefully become a new antiulcer agent.

Compound 3 (deoxoqinghaosu) and compound 4 (deoxocarbaqinghaosu) were synthesized from arteannuic acid (2). Primary exploration of their antimalarial effect against K173 strain of Plasmodium berghei shows that compound 3 is somewhat more effective than the natural compound--qinghaosu. However, the carba-analogue compound 4 is almost ineffective. The enhanced activity of compound 3 is supposedly ascribed to its higher lipophilicity and, hence, higher affinity for plasmodial membrane. Further studies are in progress.