Evaluation of the phosphodiesterase 3 inhibitor ORG 9935 as a contraceptive in female macaques: initial trials.

Contraception
Jeffrey T JensenMary B Zelinski

Abstract

The study was conducted to determine whether a phosphodiesterase (PDE) 3 inhibitor has potential as a novel contraceptive in primates. Regularly cycling adult female cynomolgus macaques of proven fertility (n=16) were treated for 7 months with placebo (controls) or the PDE3 inhibitor ORG 9935 as a daily food treat (150 mg/kg) or as a weekly depot injection (150 mg/kg, sc). After 1 month, a male of proven fertility was introduced into each group. Females underwent weekly monitoring of progesterone (P) and ultrasound evaluation for pregnancy if P remained elevated (1.0 ng/mL) >3 weeks. ORG 9935 values were evaluated using high-performance liquid chromatography. Overall, the pregnancy rate in ORG 9935-treated monkeys (4/8, 50%) did not differ from controls (7/8, 88%; p=.5). However, no animal became pregnant in a cycle when the serum level of ORG 9935 exceeded 300 nmol/L. Moreover, two treated monkeys who mated throughout the treatment phase and did not conceive became pregnant within four cycles after stopping ORG 9935. The other two animals were discontinued prematurely from the protocol. These results demonstrate that ORG 9935 may prevent pregnancy in primates at serum concentrations above 300 nmol/L and that the effect is reve...Continue Reading

References

Nov 1, 1990·Molecular Reproduction and Development·D P WolfR L Stouffer
Oct 2, 1998·Human Reproduction·M B Zelinski-WootenR L Stouffer
Jan 26, 1999·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·E MobergE Hagström-Toft
Nov 20, 2002·Expert Opinion on Investigational Drugs·Matthew A Movsesian, Rami Alharethi
May 30, 2003·Biology of Reproduction·Daniela NogueiraJohan Smitz

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Citations

Apr 26, 2015·Expert Opinion on Therapeutic Targets·Jeffrey T Jensen
Oct 23, 2012·Contraception·Ahmed M Taiyeb AlbarzanchiDuane C Kraemer
Oct 20, 2015·Life Sciences·Ahmed M TaiyebMundhir T Ridha-Albarzanchi
Oct 20, 2012·Journal of Medical Primatology·Elizabeth MicksJeffrey Jensen
Aug 16, 2016·Fertility and Sterility·Diana L Blithe
Jun 21, 2020·Biology of Reproduction·Daniel S Johnston, Erwin Goldberg
Sep 24, 2016·Journal of Cellular Biochemistry·Anumegha GuptaShail K Chaube

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