Disease relevance of Cetiedil

• Cetiedil has been reported to relieve painful crises in sickle cell anemia and to have antisickling properties in vitro [1].
• Cetiedil, at its highest dosage (0.4 mg/kg body weight), was found to be significantly superior to placebo both in reducing the number of painful sites present on all 4 treatment days and in shortening the total time in crisis [2].
• Cetiedil was the most effective drug in blocking exercise-induced bronchospasm of the drugs studied [3].
• Cetiedil), originally a molecule used for treatment of some vascular diseases, exhibits several pharmacological effects [4].
• Most adverse reactions to cetiedil are related to its anticholinergic properties (dryness of mouth, blurred vision, spacy feelings, disorientation) or vasodilatory effects (light-headedness, vertigo, cold extremities); these side-effects were dose-related with regard to incidence, severity and duration [5].

High impact information on Cetiedil

• Bepridil and cetiedil. Vasodilators which inhibit Ca2+-dependent calmodulin interactions with erythrocyte membranes [6].
• Two new vascular smooth muscle relaxants, bepridil and cetiedil, were found to possess specific CaM-inhibitory properties which resembled those of trifluoperazine [6].
• Effect of cetiedil on cation and water movements in erythrocytes [7].
• Because the viscosity of the erythrocyte interior and the kinetics of gelation are dependent on the concentration of hemoglobin, we postulated that cetiedil might inhibit sickling by modifying erythrocyte sodium or potassium movements in a manner that would increase cell water content and thus dilute the cell hemoglobin [1].
• PMN aggregation in response to 2 X 10(-7) M formyl-met-leu-phe (FMLP) was inhibited in a dose-dependent fashion by cetiedil concentrations ranging from 60 to 250 microM [8].

Biological context of Cetiedil

• All water movements can be accounted for by cetiedil-induced net cation movements [7].
• 9. Much greater concentrations of cetiedil and bepridil (IC50 approximately 1 mM and 77 microM respectively) were required to inhibit the loss of K+ which follows the application of angiotensin II (100 nM) to guinea-pig hepatocytes, and which occurs via Ca(2+)-activated K+ channels [9].
• Synthesis and structure-activity relationships of cetiedil analogues as blockers of the Ca(2+)-activated K+ permeability of erythrocytes [10].
• In another group of experiments devoted to measurement of vascular resistance of the hind limb, the results indicate that cetiedil, like papaverine and aminophylline, increased femoral blood flow through a decrease in resistance of the hind limb vasculature [11].
• This increase in flow could have been brought about only by redistribution of the cardiac output through differential effects on different vascular beds, since unlike papaverine and aminophylline, cetiedil does not increase cardiac output [11].

Anatomical context of Cetiedil

• Cetiedil is a potential antisickling agent whose major effect appears to be at the erythrocyte membrane [7].
• Modulation of polymorphonuclear leukocyte function by cetiedil [8].
• Progressive addition of purified rat testis calmodulin in vitro (10-150 ng calmodulin/mg membrane protein) restored hormone responsiveness in the presence of bepridil and cetiedil [12].
• We observed that ACh release was impaired only in cetiedil-treated preparations; synaptosomes treated with AH5183 behaved like the controls [13].
• Synaptic vesicles purified on a sucrose-KCl sedimentation gradient were tested for their ability to accumulate [1-14C]acetylcholine ([1-14C]ACh) in the absence and in the presence of AH5183 and cetiedil [14].

Associations of Cetiedil with other chemical compounds

• Correspondingly, 125 microM cetiedil prevented the translocation of calcium from the PMN membrane as assessed by chlorotetracycline fluorescence [8].
• Additionally, 125 microM cetiedil inhibited PMN aggregation in response to 2 X 10(-7) M FMLP, 20 ng/ml phorbol myristate acetate (PMA), and 1 X 10(-6) M A23187 by 69% +/- 18%, 72% +/- 20%, and 65% +/- 4%, respectively [8].
• Binding of labeled thyroid hormone by RBC membranes was unaffected by bepridil and cetiedil (up to 2 x 10(-4) M) [12].
• The effects of cetiedil, a vasodilatator substance with reported anticholinergic properties, were examined on cholinergic presynaptic functions at the nerve electroplaque junction of Torpedo marmorata using either synaptosomes or slices of intact tissue [15].
• A comparative study between the cardiovascular effects of cetiedil, a new vasodilator, and papaverine and aminophylline [11].

Gene context of Cetiedil

• Paralleling the effect of the drug on PMN aggregation, 125 microM cetiedil inhibited release of superoxide by 55% and decreased the number of available 3H-FMLP receptors [8].
• These results suggest that cetiedil affects the trigger mechanism of the plasma membrane to inhibit the activation of NADPH oxidase [16].
• The actions of clotrimazole and cetiedil, two drugs known to inhibit the Gardos channel, have been studied on single intermediate conductance calcium-activated potassium (IKCa) channels in inside out patches from human red blood cells, and compared with those of TEA and Ba2+ applied to the cytoplasmic face of the membrane [17].
• This action was investigated: 1.--In the rat: by measuring the P450 Cytochrome content of hepatic microsomes in rats treated with Cetiedil [18].
• NH+4 blocked the channel completely. hIK was blocked by the classical inhibitors of the Gardos channel charybdotoxin (IC50 28 nM) and clotrimazole (IC50 153 nM) as well as by nitrendipine (IC50 27 nM), Stichodactyla toxin (IC50 291 nM), margatoxin (IC50 459 nM), miconazole (IC50 785 nM), econazole (IC50 2.4 microM), and cetiedil (IC50 79 microM) [19].

Analytical, diagnostic and therapeutic context of Cetiedil

• The effects of cetiedil and its analogue MR 16728 were examined on spontaneous acetylcholine release measured with a chemiluminescent assay using choline oxidase in a synaptosomal suspension obtained from Torpedo marmorata electric organ [20].
• Tolerance of healthy adult males in intravenous infusion of cetiedil, a vasoerythroactive drug [21].
• Cetiedil, a new vasodilating drug with anticholinergic properties, was shown to be metabolised very rapidly in man after intravenous and oral administration of the 14C-compound [22].

References