Wirkung, Wirksamkeit und Risiken pflanzlicher Arzneimittel

Rats when forced to swim in a cylinder from which they cannot escape will, after an initial period of vigorous activity, adopt a characteristic immobile posture which can be readily identified. Immobility was reduced by various clinically effective antidepressant drugs at doses which otherwise decreased spontaneous motor activity in an open field. Antidepressants could thus be distinguished from psychostimulants which decreased immobility at doses which increased general activity. Anxiolytic compounds did not affect immobility whereas major tranquilisers enhanced it. Immobility was also reduced by electroconvulsive shock, REM sleep deprivation and "enrichment" of the environment. It was concluded that immobility reflects a state of lowered mood in the rat which is selectively sensitive to antidepressant treatments. Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests. Show more

The binding of a series of alkenylbenzenes to liver DNA of adult female CD-1 mice, isolated 24 h after i.p. administration of non-radioactive test compound (2 or 10 mg/mouse), was investigated by a modified 32P-post-labelling assay. The known hepatocarcinogens, safrole, estragole and methyleugenol, exhibited the strongest binding to mouse-liver DNA (1 adduct in 10 000 - 15 000 DNA nucleotides or 200 - 300 pmol adduct/mg DNA after administration of a 10 mg dose), while several related compounds, which have not been shown thus far to be carcinogenic in rodent bioassays, bound to mouse-liver DNA at 3 - 200x lower levels. The latter compounds included allylbenzene, anethole, myristicin, parsley apiol, dill apiol and elemicin. Eugenol did not bind. Low binding to mouse-liver DNA was also observed for the weak hepatocarcinogen, isosafrole. Two main 32P-labelled adducts, which appeared to be guanine derivatives, were detected for each of the binding chemicals on thin-layer chromatograms. The loss of safrole adducts from liver DNA was biphasic: a rapid loss during the first week (t 1/2 approximately 3 days) was followed by a much slower decline up to 20 weeks after treatment (t 1/2 approximately 2.5 months). Adducts formed by reaction of 1'-acetoxysafrole, a model ultimate carcinogen, with mouse-liver DNA in vitro were chromatographically identical to safrole-DNA adducts formed in vivo. Pretreatment with pentachlorophenol, a known inhibitor of sulphotransferases, inhibited the binding of safrole to mouse-liver DNA, providing further evidence that the metabolic activation of the allylbenzenes proceeds by the formation of 1'-hydroxy derivatives as proximate carcinogens and 1'-sulphoöxy derivatives as ultimate carcinogens. Show more