Role of intracellular calcium in the spermicidal action of 2‘,4’-dichlorobenzamil, a novel contact spermicide

Abstract

The Na+-Ca2+ exchanger and Ca2+-ATPase pumps reported to be present on the sperm membrane are responsible for maintaining the intracellular Ca2+ concentration that is involved in regulation of sperm function. We have investigated the role of intracellular Ca2+ in the presence of 2′,4′-dichlorobenzamil hydrochloride (benzamil), a Na+-Ca2+ exchange inhibitor, on human sperm motility. The mechanism of the complementary spermicidal action produced by a combination of benzamil and propranolol on human spermatozoa has been investigated also. When administered alone benzamil and propranolol produced a dose- and time-dependent decrease in motility of sperm in ejaculated semen and spermatozoa separated from semen. A combination of benzamil and propranolol exhibited a complementary spermicidal action, thereby resulting in dose reduction of both drugs for obtaining total immotility within 1 min of administration. An increase in the intracellular Ca2+ level was found to contribute to the spermicidal activity. Inhibition of the Na+-Ca2+ exchange system on sperm membrane by benzamil and membrane stabilization by propranolol resulted in accumulation of Ca2+ inside the sperm cells. When the two drugs were used in combination the time required for the total loss of motility of spermatozoa was significantly reduced due to a similar mechanism of action of both drugs.