"Cetiedil"

A collaborative, double-blind randomized study of cetiedil citrate in sickle cell crisis. We have recently completed a double-blind, placebo-controlled, noncrossover study, the goal of which was to determine whether cetiedil citrate (cetiedil) could affect the course of vaso-occlusive crises in sickle cell disease. Patients, who presented to the emergency room at least 4 but no more than 24 hours after the onset of a painful vasoocclusive crisis severe enough to require hospitalization, were considered candidates for the study. Each patient received either placebo or cetiedil at one of the following three dosages: 0.2, 0.3, or 0.4 mg/kg body weight. The assigned drug dosage was given as a 30 minute intravenous infusion every 8 hours for 4 consecutive days. A total of 67 patients was enrolled

Comparative bronchodilatory activity of cetiedil citrate monohydrate, theophylline, orciprenaline and placebo in adult asthmatics. In 40 patients, a seven day observation period in which oral bronchodilators and corticosteroids were eliminated, cetiedil (100 mg, t.i.d.), theophylline (200 mg, t.i.d.) or orciprenaline (20 mg, t.i.d.) and placebo (100 mg Lactose, t.i.d.) were given for one week each, according to a double blind, crossover randomized code. Wheezing scores were improved by all three active drugs. Twenty five of these patients undertook a moderate degree of exercise. Cetiedil was the most effective drug in blocking exercise-induced bronchospasm of the drugs studied. At rest, FEV1/VC was improved by theophylline, while PEFR improved after orciprenaline. Cetiedil improved both

. Other drugs: corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs); tricyclic antidepressants or hydroxyzine in conjunction with opiates; drugs with potential antisickling properties (cetiedil and pentoxiphyllin treatment evaluation associated with no change in analgesic ..

Bepridil and cetiedil. Vasodilators which inhibit Ca2+-dependent calmodulin interactions with erythrocyte membranes. Two new vascular smooth muscle relaxants, bepridil and cetiedil, were found to possess specific CaM-inhibitory properties which resembled those of trifluoperazine. Trifluoperazine, bepridil, and cetiedil inhibited Ca2+-dependent 125I-CaM binding to erythrocyte membranes and CaM to CaM. Bepridil and cetiedil bind directly to CaM since these drugs displaced [3H]trifluoperazine from sites on CaM. Inhibition of Ca2+-ATPase and binding by the drugs was not due to interference with the catalytic activity of this enzyme since: (a) neither inhibition of CaM-independent basal Ca2+-ATPase activity nor inhibition of proteolytically-activated Ca2+-ATPase activities were produced

Effect of cetiedil on cation and water movements in erythrocytes. Cetiedil is a potential antisickling agent whose major effect appears to be at the erythrocyte membrane. To test the hypothesis that cetiedil alters cation transport, we studied the effect of the drug in promoting changes in cell water (Wc), cell sodium (Nac), and cell potassium (Kc). Results are quite different depending on the presence or near absence of intracellular ATP. With fresh cells, 100 microM cetiedil causes little in the net cation or water movements compared with control cells incubated for 2 h. At cetiedil concentrations greater than 100 microM, however, net movements of sodium and potassium increase considerably, and cell swelling results from a net Nac gain that exceeds a net Kc loss. All water movements can

Effect of cetiedil, an in vitro antisickling agent, on erythrocyte membrane cation permeability. Cetiedil has been reported to relieve painful crises in sickle cell anemia and to have antisickling properties in vitro. The drug alters neither oxygen affinity nor the solubility of deoxyhemoglobin S. 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. The drug has two such effects: it inhibits the specific increase in potassium permeability that follows a rise in cytoplasmic calcium concentration and it causes a rise in passive sodium

Oxpentifylline and cetiedil citrate improve deformability of dehydrated sickle cells. Erythrocytes from 14 patients with homozygous sickle cell anaemia were treated with the calcium ionophore A23187 to induce loss of cellular potassium and water. The dehydrated cells showed a decrease in filterability (loss of deformability) through pores of 5 micron diameter. Oxpentifylline and cetiedil citrate

cells suspended at a haematocrit of 1% in a low potassium solution ([K]0 0.12-0.17 mM) at 37 degrees C. Net movement of K+ was measured using a K+-sensitive electrode placed in the suspension. 3. The concentrations (microM +/- s.d.) of the compounds tested causing 50% inhibition of K+ loss were: quinine, 37 +/- 3; cetiedil, 26 +/- 1; the cetiedil congeners UCL 1269, UCL 1274 and UCL 1495 , approximately 150, 8.2 +/- 0.1, 0.92 +/- 0.03 respectively; clotrimazole, 1.2 +/- 0.1; nitrendipine, 3.6 +/- 0.5 and charybdotoxin, 0.015 +/- 0.002. 4. The characteristics of the block suggested that compounds could be placed in two groups. For one set (quinine, cetiedil, and the UCL congeners), the concentration-inhibition curves were steeper (Hill coefficient, nH, > or = 2.7) than for the other

swollen cells. 8. The volume-activated K+ conductance was reversibly blocked by cetiedil, which caused half-maximal inhibition at 2.3 microM. Bepridil, quinine and barium were also effective, with IC50s (concentrations giving 50% maximal inhibition) of 2.7, 12 and 67 microM respectively. 9. Much greater concentrations of cetiedil and bepridil (IC50 approximately 1 mM and 77 microM respectively) were

Cell volume regulation in rat thymocytes. 1. DIOA (dihydroindenyl-oxy-alkanoic acid), a potent inhibitor of the K(+)-Cl- co-transport system, fully blocked regulatory volume decrease (RVD) in swelled rat thymocytes, with an IC50 of 2.2 +/- 0.5 x 10(-5) mol l-1 (mean +/- S.D., n = 4). Conversely, RVD was resistant to quinine, quinidine, apamin, cetiedil, amiloride, bumetanide and DIDS (4,4

was characterized by (i) a Hill slope greater than unity, (ii) sensitivity to an increase in external [K(+)], and (iii) a time course of onset that suggested use-dependence. Also, the potency of the nonquaternary compounds tested increased with their predicted lipophilicity. These findings suggested that the IK(Ca) blocking action resembles that of cetiedil rather than of clotrimazole. 5. Some quaternized members