Disease relevance of Calmidazolium

• Modulation of HT-29 human colonic cancer cell differentiation with calmidazolium and 12-O-tetradecanoylphorbol-13-acetate [1].
• The calmodulin antagonist calmidazolium stimulates release of nitric oxide in neuroblastoma N1E-115 cells [2].
• To determine whether calmodulin plays a role in neurodegeneration after ischemia, effects of the selective calmodulin inhibitors calmidazolium and W7 were studied in organotypic cultures of rat hippocampus [3].
• Ischemic brain injury in vitro: protective effects of NMDA receptor antagonists and calmidazolium [4].
• Protection of pyramidal cells in the CA1 region of the hippocampus by calmidazolium and W7 against hypoxia/hypoglycemia suggests that activation of intracellular calmodulin plays a significant role in ischemic neuronal injury [3].

Psychiatry related information on Calmidazolium

• Infusions of the calmodulin antagonist calmidazolium during the critical period prevented memory formation [5].

High impact information on Calmidazolium

• The calmodulin antagonists trifluoperazine and calmidazolium completely prevented the inhibition [6].
• ATP-induced DNA fragmentation but not ATP-induced 51Cr release can be blocked in cells pretreated with inhibitors of protein or RNA synthesis or the endonuclease inhibitor, zinc; whereas pretreatment with calmidazolium, a potent calmodulin antagonist, blocks both DNA fragmentation and 51Cr release [7].
• Phenylarsine oxide (10 micromol/L) induced an immediate and maintained NO-mediated relaxation of isolated rabbit carotid arteries, which was insensitive to the removal of extracellular Ca2+ and the calmodulin antagonist calmidazolium [8].
• A calmodulin antagonist, W7 (50 mumol/L), calmidazolium (100 mumol/L), or HT-74 (20 mumol/L), added to the intracellular solution abolished enhancement of IK by Ca2+, whereas the inactive form of the W7 analogue, W5, had no effect on IK [9].
• Using calmodulin inhibitors (W7 and calmidazolium), we found that retinoic acid-stimulated, A23187-stimulated, and thapsigargin-stimulated but not FIN-gamma-stimulated ICAM-1 were inhibited [10].

Chemical compound and disease context of Calmidazolium

• The role of calmodulin (CaM) in cellular heat injury of neuroblastoma N2A and hepatoma H35 cells has been investigated, using specific calmodulin-inhibiting drugs (Trifluoperazine, Compound 48/80 and Calmidazolium) [11].
• TFP, CPZ, and CMZ protected the erythrocytes from osmotic hemolysis [12].
• Ketamine, MK-801 or calmidazolium protects rat hippocampal energy status during in vitro ischemia [13].
• Nifedipine, verapamil, diltiazem, calmidazolium and trifluoperazine at low concentrations, protected the cells from the hypotonic hemolysis while at higher concentrations they caused lysis [14].

Biological context of Calmidazolium

• However, calmidazolium is effective in inhibiting the intracellular Ca2+ pump with an IC50 of approximately 2 microM [15].
• Perturbation of phosphorylation by 48/80 and calmidazolium may lead to enhanced Ca2+ release, thereby diminishing Ca2+ accumulation without affecting the Ca2+ uptake mechanism [16].
• Furthermore, SOX9-mediated transcriptional activation by cells expressing the A158T mutant is more sensitive to CDZ than cells expressing WT SOX9 [17].
• Our results show that calmidazolium is a high-affinity, noncompetitive inhibitor of skeletal SR CaATPase activity, and they suggest that this inhibition is based on binding to the membrane phospholipids rather than specific antagonism of enzyme activation by calmodulin [18].
• Relaxation enhancements induced by two spin-labeled calmidazolium analogues demonstrate that several methionine residues of CaM, significantly immobilized by calmidazolium binding, are in fact located at or near its binding sites [19].

Anatomical context of Calmidazolium

• The effects of a protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), and of a calmodulin antagonist calmidazolium (CZ), on a human colonic cancer cell line HT-29 were analyzed [1].
• A proton nuclear magnetic resonance and molecular modeling study of calmidazolium (R24571) binding to calmodulin and skeletal muscle troponin C [19].
• Binding of calmidazolium to SR membranes produced morphological changes seen by electron microscopy as membrane thickening and loss of resolution of surface detail [18].
• Inhibition of skeletal muscle sarcoplasmic reticulum CaATPase activity by calmidazolium [18].
• In experiments described here, we have explored this idea by testing effects of calmidazolium (CDZ), a potent calmodulin antagonist on striated muscle myofilaments regulated by cardiac TnC, skeletal TnC, and CaM [20].

Associations of Calmidazolium with other chemical compounds

• ATP-dependent Ca2+ transport activity was present in vesicles from both domains, insensitive to azide, oligomycin, oxalate, calmodulin, and calmidazolium, and virtually abolished at pH 6 [21].
• Our findings suggest that nifedipine has a greater degree of specificity for B16a-Pt cells than structurally different calcium channel blockers from other chemical classes (i.e., diltiazem and verapamil), or the two calmodulin antagonists (i.e., trifluoperazine and calmidazolium) [22].
• Equine sperm adenylate cyclase was also inhibited in a concentration-dependent manner by the CaM antagonists chlorpromazine and calmidazolium (IC50 = 400 and 50 microM, respectively) [23].
• In contrast, all agents known to affect intracellular concentrations of calcium, as confirmed in Fura-2-loaded hepatocytes (Bay K 8644, calcimycin, calmidazolium, ionomycin, or methoxamine) failed to influence the synthesis of angiotensinogen [24].
• The calmodulin inhibitor, calmidazolium, and the tyrosine kinase inhibitor, genistein, completely blocked MAPK activation by Ang II as well as by the Ca2+ ionophore A23187 [25].

Gene context of Calmidazolium

• In inside-out membrane patches, Trp4 is activated strongly by calmidazolium, an antagonist of CaM, and a high (50 microm) but not a low (5 microm) concentration of the Trp-binding peptide of the IP(3)R [26].
• Nevertheless, calmodulin antagonist calmidazolium and CaM kinase inhibitor KN-93 both had no effect on the activation of p56(lck) and ERK, whereas a pretreatment of Jurkat cells with MAP kinase kinase inhibitor P098059 was able to abrogate phosphorylation of ERK [27].
• In addition, BAPTA, calmidazolium, a calmodulin antagonist and PD98059 inhibited VEGF secretion by hypoxic HepG2 [28].
• Finally, calmidazolium, an inhibitor of calmodulin, had an enhancing effect on IFN-gamma yields when phytohemagglutinin (PHA) was the inducer and an adverse effect when A23187 was the inducer [29].
• The activation of ERK1 and 2 by increases in intracellular calcium was inhibited by calmidazolium suggesting the involvement of calmodulin in this response [30].

Analytical, diagnostic and therapeutic context of Calmidazolium

• In PKC-depleted cells, 5-HT-mediated amplification was greatly reduced after treatment with the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (acetoxymethyl)-ester or the calmodulin antagonists calmidazolium and N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide hydrochloride [31].
• Calmidazolium prevented the inhibition mediated by high K+ and high perfusion pressure and thereby restored the forskolin-induced stimulation [32].
• Fos expression in the suprachiasmatic nucleus (SCN) of rats induced by photic stimulation (300 lux, 1 h) during the early subjective night of the rats was inhibited by treatment with CMZ (10 mg/kg i.p.) or TFP (20 mg/kg i.p.) 30 min before photic stimulation [33].
• Meanwhile, intrathecal calmidazolium (10, 50, 250 microg) induced a dose-dependent analgesia [34].
• In human MG63 osteosarcoma cells, the effect of calmidazolium on [Ca(2+)](i) and proliferation was explored using fura-2 and ELISA, respectively [35].

References