An attempt was made to postpone term in 59 pregnant rats by s.c. injections of indomethacin or cyproheptadine, or a combination of both. The cyproheptadine group gave birth to their litters on days 20-22, yet indomethacin postponed labour to the 23rd day, both when given alone or in combination with cyproheptadine. As the fourth saline group went into labour on the 20--23rd day the indomethacin postponement cannot be considered significant. Indomethacin being a prostaglandin antagonist and cyproheptadine a serotinin antagonist, it may be concluded that neither prostaglandin nor serotonin are decisive for the intricate process which triggers parturition. Other factors, such as decrease of progesterone, increase of oestrogen and perhaps foetal oxytocin, as well as placental ACTH, seem to concur in inducing labour, their effect being fortified by serotonin and prostaglandins during parturition.

In three of 1,094 cases of cord complications the mothers experienced reduction of fetal movments until cessation. In these three instances the fetal heart beat was audible but changes appeared on the fetal heart rate monitor. The course of loss of fetal movements resembled that seen in cases of placental insufficiency. It is suggested that the reduced fetal movements and the changes in fetal heart rate were due to a diminished blood flow in the cord vessels as a result of gradual cord compression.

Serum prolactin values in normal pregnant women showed a progressive increase from a mean value of 50 ng/ml in the 12th week to 270 ng/ml at term, with the range at term being 100-600 ng/ml. There was a fairly good correlation (r = 0.7) between the values of 24-hour urine estriol in 138 determinations and in the serum prolactin in 133 pregnant women. The regression lines of serum hPRL values with time of gestation in cases of intrauterine growth retardation (IUGR) and diabetes mellitus were less steep than those seen in normal pregnancy. The serum hPRL value of patients with preeclamptic toxemia, latent diabetes, premature rupture of membranes, or multiple pregnancies were found not to differ significantly from the values observed in normal pregnancy. The results indicate that prolactin determinations in pathologic pregnancies are not useful as an aid in their evaluation.

Thirty-three women with preeclamptic toxemia were retrospectively divided into three groups, according to clinical data, urinary estriol excretion, fetal growth, fetal movements and fetal heart recordings. In group 1 (six patients) there was no fetal growth retardation, and fetal motor function and heart rate were normal. In group 2 (17 patients) there was fetal growth retardation, estriol values were usually low, and fetal movements and heart rate were normal. In group 3 (10 patients) fetal movements decreased markedly almost until complete cessation for 12 to 24 h, and pathological changes were present in fetal heart recordings. A classification of preeclamptic toxemia according to these criteria is suggested. Patients who manifest placental metabolic failure, such as the women in group 2, should be hospitalized for observation only, as no immediate danger to the fetus is apparent. If there are signs of severe fetal distress and cardiomotor failure, such as in group 3, prompt delivery is essential to prevent fetal death in utero.

Invitro experiments with strips of pregnant rat uterus, normal estrogen-primed rat uterus and duodenum showed that cyproheptadine HCl (Periactin®), a serotonin antagonist, inhibits the intensity of spontaneous contractions of these muscle strips. The degree of inhibition depends upon the concentration of cyproheptadine. Contraction frequency was also reduced in these smooth muscles, the basic tonus not being affected. Addition of serotonin (5-HT) to the water bath increases the intensity of muscle contractions. Cyproheptadine inhibits this increase at smaller doses than those required for inhibiting spontaneous contractions. Whereas cyproheptadine does not inhibit completely the pace-maker rhythm of the muscle cells, it suppresses the amplitude of their contractions.

Among the causes leading to habitual abortion, psychogenic factors and emotional stress are known to play an important role (1,2).

SUMMARY Subcutaneous injection of the 5-hydroxytryptamine (5-HT) antagonist cyproheptadine hydrochloride (Periactin) produced a significant decrease in uptake of [14C]5-HT (serotonin) in the myometrium and to a lesser degree in the ovaries, foetuses and heart of pregnant rats. This effect of cyproheptadine was considerably increased in rats pretreated with the monoamine oxidase inhibitor pargyline hydrochloride. These results suggest that the anti-abortive effect of cyproheptadine is based on specific inhibition of the contractile effect of 5-HT on the myometrium. The hypothesis is advanced that cyproheptadine competes with serotonin for its receptors and thus blocks the effect of serotonin.

Intra-amniotic injection of pregnant rat mothers with pargyline HCl (Eutonyl), a MAO blocker, produces fetal death through activation of endogenous serotonin. In the present paper 5 progesterone derivatives were tested for their capacity to prevent serotonin abortion. While progesterone, dydrogesterone, medroxy-progesterone acetate and allylestrenol were not effective in preventing serotonin abortion, treatment with the retroprogesterone trengestone (RO 4-8347) prevented abortion and premature delivery in the 2nd and 3rd trimesters, though it could not prevent serotonin abortion in rats in the 1st trimester. The fetus-saving effect of trengestone appears to be due to the fact that it increases formation of serotonin-metabolizing enzymes, including MAO in the endometrium, whereas estrogens decrease it.