The mode of inhibition of human erythrocyte membrane-bound acetylcholinesterase by cisplatin in vitro.

The effect of the well known anticancer drug "cisplatin" on the human erythrocyte membrane-bound acetylcholinesterase (AChE) has been investigated. It was found that cisplatin has inhibitory activity against AChE. Cisplatin (0.5-7.0 mM) inhibited AChE activity (27-82%) in a concentration dependent manner. The nature of the inhibition of AChE by cisplatin was complex and involved a partial reversible stage followed by a slow acting irreversible step. The inhibition was independent of a preincubation period up to 90 min while becoming dependent after this period. By diluting the preincubated AChE-cisplatin mixture for different times (0-24 h), the inhibition was partially reversed but again increased progressively with incubation time, ultimately reaching complete inhibition. The effect of increasing substrate concentration had the same behaviour as the dilution effect.