Ovulation blockade through synergism of cycloheximide with assorted anesthetics

This report addresses the following question: Can ovulation be blocked through a combined action of two drugs, which individually have no effect on ovulation. Ovulation blockade in hamsters was achieved through synergism of two drugs that individually had no effect on ovulation. Treatments were given at 18:00 h on pro-estrus. The keystone finding was that cycloheximide (CX), in a dose too small to affect ovulation, can be made to block ovulation by pretreating hamsters 15 min earlier with pentobarbital. Ovulation blockade was also achieved with phenobarbital + CX, ketamine + CX, and ether + CX. When given alone, none of the four anesthetics interfered with ovulation. The mechanism by which the anesthetic/CX synergism works is not known. The pituitary can be excluded as a target, because it is not necessary for ovulation after 15:30 on pro-estrus. It is speculated that CX reduces the synthesis of ovarian proteins needed for follicle rupture, and the anesthetics augment this process through action on either the ovary, the brain, the liver, or a combination thereof.