Further studies on the interaction of loperamide with capacitative calcium entry in Leukemic HL‐60 cells

Abstract

Loperamide at 3–10 µM has augmentative effects on calcium levels elevated by capacitative calcium entry (CCE) in leukemic HL‐60 cells after release of intracellular calcium by ATP or thapsigargin (Harper et al. [1997] Proc Natl Acad Sci USA 94:14912–14917). The effect of loperamide on calcium levels was absent at a pH value of 6.8, a pH at which CCE is not active in HL‐60 cells. Further investigations of HL‐60 cells in recent years revealed a great reduction in the magnitude of the loperamide response. However, when preceded by a CCE blocker, namely N‐methylnitrendipine (MRS 1844) or N‐propargylnitrendipine (MRS 1845), loperamide caused a significant reversal of the blockade. Six structural analogs of loperamide were synthesized, but only two showed loperamide‐like activity. Drug Dev. Res. 67:842–851, 2006. Published 2007 Wiley‐Liss, Inc.

Loperamide‐induced cardiotoxicity in rats: Evidence from cardiac and oxidative stress biomarkers

“…Interaction of calmodulin with calcium is an important step in the pathway leading to water and electrolytes transport across the intestine. Thus, loperamide can alter bowel function by modulating the binding of calcium‐activated calmodulin complex with its receptor . Despite this pharmacological activity, there are reported cases of abuse and misuse because of its opioid properties …”