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Tuesday September 25 2018

Ouabain: From Poison To Contraceptive

Despite the myriad of contraceptive methods designed for women, the options for men have generally relied on vasectomy or use of condoms.1 Recently, however, researchers from the American Chemical Society have investigated the potential of introducing a third option based on analogs of ouabain, a plant-derived cardiovascular toxin traditionally used as a poison.2,3

Ouabain inhibits Na+/K+-ATPase, a protein expressed in almost all vertebrate cells in various isoforms to maintain a resting membrane potential.4,5 The purpose of this protein is to maintain resting membrane potential through sodium/potassium homeostasis. Of particular interest is the α4 isoform located only in mature sperm cells, where its activity maintains homeostatic conditions necessary for sperm survival.5 Despite these attributes, ouabain remains a poor candidate for contraception due to serious clinical consequences of Na+/K+-ATPase inhibition, which may include hyperkalemia, cardiac arrhythmias, or death.5

In a study published in The Journal of Medicinal Chemistry, 32 heterogeneous ouabain analogs were created.2 In vitro experiments with rat sperm revealed that the analogue with the highest affinity for the α4 isoform caused a reduction in the motility of sperm, hindering its ability to reach the egg.2 The drug also decreased hyperactivation, compromising the sperm’s ability to penetrate the zona pellucida, a thick membrane surrounding the egg.2 Furthermore, in vivo experimentation revealed that oral administration to rats had no toxic effects and reduced both sperm count and motility.2

Despite these promising results, additional experiments are required, especially considering the potentially dangerous clinical consequences of ouabain and its inhibition of Na+/K+-ATPase. Further research on the ouabain analog’s safety, as well as its exact mechanism of action and its efficacy in human subjects will be needed to confirm or reject the possibility of a male contraceptive derived from this plant extract.

Written by Kevin Chen

References may be found in the journal.

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