Sperm immobilizing potency of amitriptyline and imipramine: measured with transmembrane migration

Abstract

The inhibitory effect of amitriptyline and imipramine on human sperm motility was measured in vitro with a transmembrane migration method. The EC50 for amitriptyline and imipramine were 170 microM and 160 microM respectively. They were more potent than any other drug that had been tested on this pharmacological model. Transmembrane migration method was less sensitive than turbidimetric method to detect the sperm immobilizing effect of drugs.

PIP: The sperm immobilizing effect of 2 frequently prescribed antidepressants--amitriptyline and imipramine--was measured with a transmembrane migration method. Results were compared with those obtained by torbidimetric method. In addition, the potencies of these 2 drugs were compared with other sperm immobilizing agents, so the underlying mechanism and clinical implication could be elucidated. Fresh human semen samples were collected from healthy donors. Drug treated sperm motility was calculated from the proportion of sperm that moved across the membrance from semen drug mixture into phosphate buffered saline during 2 hour incubation at 37 degrees Centigrade. The motility of sperm in semen mexed with phosphate buffered saline was used as control. The drug treated sperm motility was expressed as percentage of control and plotted on a semilog paper. The concentration of drug that decreased sperm motility of 50% of control (EC50) was obtained from the concentration response curve. The EC50 for amitriptyline and imipramine were 170 mcgM and 160 mcgM, respectively. The difference between these 2 drugs at all concentrations was not significant. The clinical implication for determing the sperm immobilizing potency of drugs in vitro is uncertain at this time. The EC50 is nearly a hundred times higher than the therapeutic blood levels of these drugs. In addition, such an in vitro test investigates the acute effect of drugs only; longterm effect, as well as the effect of the metabolites, were not included. The potential value of developing sperm motility as a cellular model for pharmacological research is confirmed in this study.