Cilostazol blocks pregnancy in naturally cycling mice.
BACKGROUND
Administration of a phosphodiesterase three enzyme inhibitor (PDE3-I) in rodents and primates results in ovulation of immature oocytes. Concerns regarding inhibition of PDE3 enzymes that are expressed in heart and blood vessels discouraged further development of PDE3-Is as nonsteroidal contraceptives. Cilostazol (CLZ) is a PDE3A-I that is approved for medical indications in humans and has an additional effect of adenosine uptake inhibition that is believed to counterbalance the undesirable outcomes resulting from PDE inhibition.


METHODS
Cycling mature female mice were treated with 7.5 or 15 mg CLZ, dimethyl sulfoxide or water beginning on the day of proestrus. Animals were placed with fertility-proven males after 3 days of treatment. Treatments were continued until 1 day after detection of a vaginal plug, and then females were monitored up to 30 days postbreeding to assess the effects of the compounds on pregnancy. Each of the treated female with CLZ was then remated with the same male and again monitored up to 30 days.


RESULTS
None of the CLZ-treated mice produced offspring, whereas all of the control animals maintained pregnancy and delivered normal pups (p<.0001). Remating of the previously CLZ-treated females exhibited normal pregnancies and gave birth to live offspring that were not different from the controls.


CONCLUSIONS
CLZ is a potential nonsteroidal contraceptive agent that merits further evaluation in other mammals.
Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. aridha@cvm.tamu.edu
Ahmed M Taiyeb
AM
Albarzanchi
Christie M
CM
Sayes
Mundhir T
MT
Ridha Albarzanchi
Virginia R
VR
Fajt
W Les
WL
Dees
Duane C
DC
Kraemer
D000818:Animals; D000077407:Cilostazol; D003270:Contraceptive Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology*; D011247:Pregnancy / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*
D003270:Contraceptive Agents; D058987:Phosphodiesterase 3 Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol