Document Detail


Evaluation of the phosphodiesterase 3 inhibitor ORG 9935 as a contraceptive in female macaques: initial trials.
MedLine Citation:
PMID:  20103457     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The study was conducted to determine whether a phosphodiesterase (PDE) 3 inhibitor has potential as a novel contraceptive in primates.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: These results demonstrate that ORG 9935 may prevent pregnancy in primates at serum concentrations above 300 nmol/L and that the effect is reversible.
Authors:
Jeffrey T Jensen; Richard L Stouffer; Jessica E Stanley; Mary B Zelinski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-11-06
Journal Detail:
Title:  Contraception     Volume:  81     ISSN:  1879-0518     ISO Abbreviation:  Contraception     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-27     Completed Date:  2010-03-31     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0234361     Medline TA:  Contraception     Country:  United States    
Other Details:
Languages:  eng     Pagination:  165-71     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA. jensenje@ohsu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Contraceptive Agents, Female / therapeutic use
Dose-Response Relationship, Drug
Female
Fertility / drug effects*
Macaca fascicularis
Male
Phosphodiesterase Inhibitors / therapeutic use*
Pregnancy
Thiophenes / blood,  therapeutic use*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
P51 RR000163-496059/RR/NCRR NIH HHS; R01 HD042710-04/HD/NICHD NIH HHS; R01-042710//PHS HHS; RR00163/RR/NCRR NIH HHS; U54 HD 031398/HD/NICHD NIH HHS; U54 HD018185-249001/HD/NICHD NIH HHS; U54 HD18185/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Contraceptive Agents, Female; 0/Phosphodiesterase Inhibitors; 0/Thiophenes; 129425-83-8/Org 9935
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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