Spermicidal Activity of Sulfonylureas and Meglitinide Analogues: Role of Intrasperm Ca2+ Elevation

Intrasperm calcium concentration ([Ca2+]is) is known to play a vital role in regulating motility and viability of ejaculated spermatozoa. K ATP channel blockers are reported to block K ATP channels, leading to depolarization of the cell membrane. This activates the voltage-gated calcium channels, resulting in enhanced Ca2+ influx, which eventually elevates the intracellular [Ca2+] level. Hence, it can be hypothesized that drugs acting on K ATP channels could possess the ability to elevate [Ca2+]is. Sulfonylureas such as glibenclamide or gliclazide, as well as meglitinide analogues such as repaglinide, produced a dose- and time-dependent decrease in viability, each requiring 7.5 mM, 10 mM and 6.5 mM, respectively, to produce death of all sperm cells immediately upon addition to ejaculated human semen samples. The reduction in sperm viability was accompanied by an elevation of [Ca2+]is and was affected by removal of extracellular Ca2+. Significantly (P < 0.05) less time was required to elevate [Ca2+](is) and produce complete loss of sperm viability when any of these drugs were added to sperm cells simultaneously with selected agents affecting Ca2+ homeostasis. Thus, the spermicidal activity of these drugs attributed to elevation of [Ca2+]is and their synergism can be potentially exploited for developing contact spermicidal formulations.