Termination of pregnancy in cases of intrauterine fetal death, missed abortion, molar and anencephalic pregnancy with intramuscular administration of 2a 2b dihomo 15(S) 15 methyl PGF2 alpha methyl ester--a multicentre study.

2a 2b dihomo 15(S) 15 methyl PGF2 alpha methyl ester (dihomo 15 me PGF2 alpha) in intramuscular doses of 0.5 mg 8 hourly was used in 631 patients with abnormal intrauterine pregnancy comprising 282 cases of intrauterine fetal death, 233 cases of missed abortion, 34 and 82 cases respectively anencephalic and molar pregnancies. The study was carried out as a collaborative project between the University Departments of Obstetrics and Gynaecology in Singapore (Singapore), Medan (Indonesia) and Kuala Lumpur (Malaysia) during the period June 1974 and November 1979. Six hundred patients (95.1%) aborted or delivered in a mean time of 11.3 hours (S.D. +/- 7.0) with an average of 1.8 injections of the prostaglandin analogue per patient. Side effects included vomiting (23.6%; mean 0.45 episodes per patient), diarrhoea (44.4%; mean 1.00 episode per patient), cold and shivering (11.9%) and pyrexia (12.4%). One patient sustained a cervical laceration which did not require repair. There were no complications.

Inhibition of the monkey corpus luteum with 15-methyl prostaglandins.

The corpus luteum inhibiting properties of eighteen 15-methyl prostaglandin analogs were determined in the rhesus monkey during concomitant stimulation of the corpus luteum with chorionic gonadotropin. The methyl ester of (15S)-15-methyl PGF2 alpha (15M-PGF2 alpha, 12.5 mg/monkey) lowered serum progesterone to 12% of pretreatment values within 24 hours, however progesterone returned to normal limits within 48 hours. Elongation of the top side-chain by two carbons (2a,2b-dihomo-15M-PGF2 alpha methyl ester, 13 mg/monkey), substitution of a hydroxymethyl group at carbon 1 (2-decarboxy-2-hydroxymethyl-15M-PGF2 alpha, 12 mg/monkey), or the formation of the carbon 1 amide (15M-PGF2 alpha amide, 12.5 mg/monkey) improved the inhibitory activity of 15M-PGF2 alpha; serum progesterone for these 3 analogs was depressed to 15-30% of pretreatment levels within 24 hours, and did not return to control values. Luteal function was not inhibited (12 or more mg/monkey) when the 15-methyl group was placed in the R configuration, the top side chain was shortened by two carbons, an amino group was substituted for carbon 1, the 5-oxa modification was added, or the 1,9-lactone was formed. Some other modifications of 15M-PGF2 alpha were also inactive, although not all were tested at equivalent doses: 2,2-difluoro; 4,5-cis-didehydro; 9,11-dideoxy-9 alpha, 11 alpha-dichloro; 11-deoxy; 17-phenyl; 1,15-lactone; and the p-benzamidophenyl ester of 2a,2b-dihomo-15M-PGF2 alpha. (15S)-15-Methyl PGE2 methyl ester (1 mg/monkey) depressed serum progesterone concentrations to 42% of pretreatment values within 24 hours; 2a,2b-dihomo-11-deoxy-(15S)-15-methyl PGE2 methyl ester was inactive (5 mg/monkey). A corpus luteum inhibiting action of certain 15-methyl prostaglandins can be demonstrated in the rhesus monkey.

Opposite and mutually antagonistic effects on uterine contractility of two epimeric forms of a synthetic prostaglandin analog.

Comparisons were made of the ability of intravenous infusions of prostalene and PGF2 alpha to stimulate increases in uterine contractility in vivo in the 14 day pregnant hamster. Whereas PGF2 alpha gave a linear dose response over the range 0.25 to 6.25 microgram/min., to achieve 5 fold increase in uterine activity, prostalene induced a multiphasic dose response curve. Inhibition was observed at 0.01 microgram per min. followed by a shallow stimulatory dose response to 0.25 microgram/min. plateauing at 1.8 fold stimulation to at least 1.25 microgram per min. When the epimeric mixture was separated and the two 15 position epimers studied separately the reason for this atypical dose response curve became clear. The 15 alpha OH epimer induced a linear stimulatory dose response from 0.05 to 6.25 microgram per min. infusion rates to a 5 fold increase in uterine contractility. The 15 beta OH epimer, however, induced a linear inhibitory dose response over the range 0.4 to 50 ng/min. It was, therefore, apparent that the atypical dose response curve observed from the mixture was the resultant of two opposite and mutually antagonistic activities. The data suggests also that the inhibitory epimer is capable of antagonizing both endogenous and exogenous prostaglandin, probably by a mechanism of competitive inhibition.