scholarly journals Investigation of Calcium Channel Blockers as Antiprotozoal Agents and Their Interference in the Metabolism ofLeishmania (L.) infantum

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Juliana Quero Reimão ◽  
Juliana Tonini Mesquita ◽  
Daiane Dias Ferreira ◽  
Andre Gustavo Tempone
Keyword(s):  
Calcium Channel ◽  
Chagas Disease ◽  
Calcium Channel Blockers ◽  
Channel Blockers ◽  
Antiprotozoal Activity ◽  
Additive Interaction ◽  
Therapeutic Class ◽  
Species Production

Leishmaniasis and Chagas disease are neglected parasitic diseases endemic in developing countries; efforts to find new therapies remain a priority. Calcium channel blockers (CCBs) are drugs in clinical use for hypertension and other heart pathologies. Based on previous reports about the antileishmanial activity of dihydropyridine-CCBs, this work aimed to investigate whether thein vitroanti-Leishmania infantumand anti-Trypanosoma cruziactivities of this therapeutic class would be shared by other non-dihydropyridine-CCBs. Except for amrinone, our results demonstrated antiprotozoal activity for fendiline, mibefradil, and lidoflazine, with IC50values in a range between 2 and 16 μM and Selectivity Index between 4 and 10. Fendiline demonstrated depolarization of mitochondrial membrane potential, with increased reactive oxygen species production in amlodipine and fendiline treatedLeishmania, but without plasma membrane disruption. Finally,in vitrocombinations of amphotericin B, miltefosine, and pentamidine againstL. infantumshowed in isobolograms an additive interaction when these drugs were combined with fendiline, resulting in overall mean sum of fractional inhibitory concentrations between 0.99 and 1.10. These data demonstrated that non-dihydropyridine-CCBs present antiprotozoal activity and could be useful candidates for futurein vivoefficacy studies against Leishmaniasis and Chagas’ disease.

Interaction between organic calcium-channel blockers and taurine in vitro and in vivo

1982 ◽  
Vol 34 (5) ◽  
pp. 329-330 ◽  
Author(s):  
F. Franconi ◽  
I. Stendardi ◽  
F. Martini ◽  
L. Zilletti ◽  
A. Giotti
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Channel Blockers

Inhibition by dihydropyridine class calcium channel blockers of tumor cell-platelet-endothelial cell interactions in vitro and metastasis in vivo

1985 ◽  
Vol 34 (2) ◽  
pp. 235-241 ◽  
Author(s):  
Kenneth V. Honn ◽  
James M. Onoda ◽  
Kim Pampalona ◽  
Marjorie Battaglia ◽  
Gregory Neagos ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Tumor Cell ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Cell Interactions ◽  
Channel Blockers

Potentiation of vincristine effect in human and murine gliomas by calcium channel blockers or calmodulin inhibitors

1985 ◽  
Vol 63 (6) ◽  
pp. 905-911 ◽  
Author(s):  
Keizo Kaba ◽  
Eiichi Tani ◽  
Tatsuo Morimura ◽  
Tsuyoshi Matsumoto
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Channel Blockers ◽  
Human Glioblastoma ◽  
Content Type ◽  
Rat Glioma ◽  
Calmodulin Inhibitors ◽  
Outward Transport

✓ The effects of calcium channel blockers and calmodulin inhibitors on vincristine cytotoxicity were studied in vitro with five glioma cell lines: three human glioblastomas, one rat glioma, and one mouse ependymoblastoma. One human glioblastoma and the rat glioma were resistant to vincristine in contrast to other glioma cells. The resistance to vincristine was considerably decreased by nontoxic or marginally toxic concentrations of calcium channel blockers or calmodulin inhibitors, although the former was more effective than the latter. In the presence of verapamil, the vincristine cytotoxicity, as measured by cell doubling times, increased 90- and 84-fold in the vincristine-resistant human glioblastoma and rat glioma, respectively. The decrease in the resistance to vincristine was related to a marked increase in the intracellular level of that drug, probably mediated by inhibiting its outward transport. The in vivo studies showed that verapamil or nicardipine administered daily with vincristine for 10 days significantly enhanced the chemotherapeutic effect of vincristine in an intracranially transplanted rat glioma model. An approximately 32% to 118% increase in life span occurred with 15 mg/kg/day of verapamil, depending on the doses of vincristine.

Praziquantel and the benzodiazepine Ro 11-3128 do not compete for the same binding sites in schistosomes

Parasitology ◽  
2007 ◽  
Vol 135 (1) ◽  
pp. 47-54 ◽  
Author(s):  
L. PICA-MATTOCCIA ◽  
A. RUPPEL ◽  
C. M. XIA ◽  
D. CIOLI
Keyword(s):  
Calcium Channel ◽  
Binding Sites ◽  
Calcium Influx ◽  
Cytochalasin D ◽  
The Other ◽  
Channel Blockers ◽  
Spastic Paralysis ◽  
Receptor Sites

SUMMARYThe benzodiazepine Ro 11-3128 (methyl-clonazepam) presents several similarities with praziquantel with regard to its anti-schistosomal mode of action, since both drugs cause spastic paralysis, calcium influx and tegumental disruption in the parasites. In order to know whether the two compounds share the same binding sites in the schistosomes, we performed in vivo and in vitro competition experiments. We took advantage of the fact that Ro 11-3128 is active against immature Schistosoma mansoni (whereas praziquantel is inactive), and praziquantel is active against S. japonicum (which is insensitive to Ro 11-3128). An excess of praziquantel did not inhibit the activity of Ro 11-3128 against immature S. mansoni and an excess of Ro 11-3128 did not inhibit the activity of praziquantel against S. japonicum, suggesting that the schistosome binding sites of the two drugs are different. On the other hand, cytochalasin D, an agent known to perturb – among other things – calcium channel function, was capable of inhibiting the schistosomicidal activity of both praziquantel and Ro 11-3128, thus adding another element of similarity between the two anti-schistosomal agents. A similar, albeit partial, inhibition of the schistosomicidal activity of the two drugs was exerted by some of the classical calcium channel blockers. Taken together, these results suggest that praziquantel and Ro 11-3128, although binding to different schistosome receptor sites, may use the same basic anti-schistosomal effector mechanisms.

Growth inhibition of human cancer cells in vitro by T-type calcium channel blockers

2006 ◽  
Vol 16 (19) ◽  
pp. 5014-5017 ◽  
Author(s):  
Jae Yeol Lee ◽  
Seong Jun Park ◽  
Sung Jun Park ◽  
Min Joo Lee ◽  
Hyewhon Rhim ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Calcium Channel ◽  
Cancer Cells ◽  
Calcium Channel Blockers ◽  
Human Cancer ◽  
Channel Blockers ◽  
Human Cancer Cells
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