Contraceptive activity of a spermicidal aryl phosphate derivative of bromo-methoxy zidovudine (compound WHI-05) in rabbits.
WHI-05 (5-bromo-6-methoxy-5,6-dihydro-3'-azidothymidine-5'-(p-methoxyphenyl) methoxyalaninyl phosphate, CAS 213982-93-5) is a highly promising anti-viral and spermicidal agent with clinical potential as a vaginal contraceptive which can prevent the sexual transmission of AIDS. In this study, the contraceptive activity of WHI-05 in rabbits was evaluated. Exposure of semen to WHI-05 at the time of artificial insemination inhibited pregnancy and embryo implantation by 90%. Intravaginal application of 2% WHI-05 containing gel also inhibited the pregnancy rate by 90%. WHI-05 had no side effects for the offspring of rabbits who became pregnant despite WHI-05.
D'Cruz
Osmond J
OJ
Drug Discovery Program, Department of Reproductive Biology, Parker Hughes Institute, Paradigm Pharmaceuticals, LLC, St. Paul, MN, USA. odcruz@ih.org
Uckun
Fatih M
FM
D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003272:Contraceptive Agents, Male / Q000737:chemistry / Q000494:pharmacology*; D054306:Dideoxynucleotides; D004655:Emulsions; D005260:Female; D005298:Fertility / Q000187:drug effects; D005782:Gels; D007315:Insemination, Artificial; D008098:Litter Size; D008297:Male; D011247:Pregnancy; D011817:Rabbits; D013089:Spermatocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D013534:Survival; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
C114569:5-Bromo-6-methoxy-5,6-dihydro-3'-azidothymidine-5'-(p-methoxyphenyl)methoxyalaninyl phosphate; D019380:Anti-HIV Agents; D003272:Contraceptive Agents, Male; D054306:Dideoxynucleotides; D004655:Emulsions; D005782:Gels; D013089:Spermatocidal Agents; D013938:Thymidine Monophosphate; D015215:Zidovudine