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Flückiger E, Salzmann R.
“Serotoninantagonismus an der Placenta ”.
Experientia. 1961;17:131.
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Abstract
In pregnant rats and mice, serotonin (5-HT), in doses which do not cause infarction in other organs, produces infarcts in the placenta. Placental ischemia leads to death of the fetus within 3 to 4 hours. This well-defined effect can be used for comparative evaluation of 5-HT antagonists. . This test (in mice 15 mg/kg 5-HT s.c.) was employed to compare the activities of LSD, substance PML 946 (1-methl-d-lysergic acid propanolamide) and UML (1-methyl-D-lysergic acid butanoloamide). Determination of the s.c. ED50 (dose affording 500rotection) yielded the following values: LSD 30 mcg/kg, PML 946 9 mcg/kg, UML 3.7 mcg/kg. Thus UML was about 8 times more effective than LSD and about 2.5 times more active than PML 946. . For inhibition of 5-HT-induced edema of the rat's paw the activity ratios of LSD: PML 946: UML were 1 : 2.6 : 4.4 (Doepfner & Cerletti, Arch.Allergy 12: 89 (1958)). In the isolated rat uterus the activity ratio of LSD : UML was 1 : 4 (Fanchamps et al., Schweiz.med.Wchnschr. 90: 1040 (1960). In comparison with these test objects the increase in 5-HT antagonism due to l-methylation of D-lysergic acid is particularily marked in the placenta. This is also demonstrated by the dose antagonist: dose antagonist ratio which, for the ED50 of UML in the placenta, is 1 : 4000.
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