Effect of Flunarizine, a Calcium Channel Blocker, on Intraocular Pressure and Aqueous Humor Dynamics in Monkeys

Wang, Rongfang; Gagliuso, D.J.; Podos, Steven M.

doi:10.1097/ijg.0b013e318133a845

Cited by 22 publications

(16 citation statements)

References 32 publications

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“…However, the results need to be interpreted with caution as discussed below. First, several Ca 2ϩ channel antagonists have been demonstrated to lower intraocular pressure (IOP) [18][19][20] and the blockade of Ca 2ϩ channels in neuronal cells could influence the release of Flunarizine dilated retinal blood vessels. In this case, the diameters of blood vessels in the selected regions were measured.…”

Section: Discussionmentioning

confidence: 99%

Vasodilator Effects of Flunarizine on Retinal Blood Vessels in Anesthetized Rats

Noguchi

Mori

Sakamoto

et al. 2009

Biological & Pharmaceutical Bulletin

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The aim of this study was to investigate the effects of intravenous administration of flunarizine on the diameter of retinal blood vessels and blood pressure in anesthetized rats and to compare the effects of this antagonist with those of nicardipine and nifedipine. Retinal vascular images were captured with a fundus camera system for small animals and the diameter of retinal blood vessels contained in the images was measured using imageprocessing softwares on a personal computer. Blood pressure was continuously measured. Flunarizine [1-30 m mg/kg, intravenously (i.v.)] dose-dependently increased the diameter of retinal blood vessels without significantly changing systemic blood pressure. Nicardipine (1-30 m mg/kg, i.v.) increased the retinal blood vessel diameter but decreased blood pressure in a dose-dependent manner. Nifedipine (10-100 m mg/kg, i.v.) failed to dilate the retinal blood vessels, although it produced comparable depressor responses as those to nicardipine. These results suggest that flunarizine selectively acts on the retinal blood vessels rather than on the peripheral resistance vessels. Flunarizine could therefore be considered as a candidate for therapeutic drugs to treat diseases associated with disorders of retinal circulation without severe cardiovascular side-effects.

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Section: Discussionmentioning

confidence: 99%

Vasodilator Effects of Flunarizine on Retinal Blood Vessels in Anesthetized Rats

Noguchi

Mori

Sakamoto

et al. 2009

Biological & Pharmaceutical Bulletin

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“…channel blocker that has been used to prevent migraine headaches [1], control intraocular pressure [2], and eliminate atrial flutter [3]. In addition, flunarizine possesses cytoprotective activity in some model systems.…”

Section: Introductionmentioning

confidence: 99%

The Ca2+ channel blocker flunarizine induces caspase-10-dependent apoptosis in Jurkat T-leukemia cells

Conrad¹,

Furlong²,

Doucette³

et al. 2010

Apoptosis

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Flunarizine is a Ca(2+) channel blocker that can be either cytoprotective or cytotoxic, depending on the cell type that is being examined. We show here that flunarizine was cytotoxic for Jurkat T-leukemia cells, as well as for other hematological maligancies, but not for breast or colon carcinoma cells. Treatment of Jurkat cells with flunarizine resulted in caspase-3 activation, poly (ADP-ribose) polymerase cleavage, and laddering of DNA fragments, all of which are hallmarks of apoptosis. Flunarizine-induced DNA fragmentation was inhibited by the caspase-3 inhibitor z-DEVD-fmk, the caspase-8/caspase-10 inhibitor z-IETD-fmk, and the caspase-10 inhibitor z-AEVD-fmk, but was not reduced in caspase-8-deficient Jurkat cells, indicating the involvement of caspase-10 upstream of caspase-3 activation. Interestingly, FADD recruitment to a death receptor was not involved since flunarizine caused DNA fragmentation in FADD-deficient Jurkat cells. Flunarizine treatment of Jurkat cells also resulted in reactive oxygen species production, dissipation of mitochondrial transmembrane potential, release of cytochrome c from mitochondria, and caspase-9 activation, although none of these events were necessary for apoptosis induction. Collectively, these findings indicate that flunarizine triggers apoptosis in Jurkat cells via FADD-independent activation of caspase-10. Flunarizine warrants further investigation as a potential anti-cancer agent for the treatment of hematological malignancies.

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“…These alterations result in modulation of mitochondrial function (i.e., calcium overload, phospholipase activation and inhibition of respiratory chain function) leading to ATP depletion, DNA fragmentation and irreversible injury of the target organ [17,54]. Flunarizine has been used to prevent migraine headaches, control intraocular pressure, eliminate atrial flutter, inhibits membrane lysis and DNA fragmentation in explanted embryonic rat ventral mesencephalic cells, and it protects auditory cells against the cytotoxic effects of cisplatin [55,56]. Recently, it has been documented that it possesses a renoprotective role against gentamicin-induced nephrotoxicity via mitochondrial permeability transition pore inactivation [19].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Dependent Apoptosis: Ameliorative Effect of Flunarizine on Ischemia–Reperfusion of Celiac Artery-Induced Gastric Lesions in the Rat

2011

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Effect of Flunarizine, a Calcium Channel Blocker, on Intraocular Pressure and Aqueous Humor Dynamics in Monkeys

Abstract: Flunarizine reduces IOP in a dose-dependent manner when administered to glaucomatous monkey eyes, but also has an ocular hypotensive effect on the contralateral untreated eyes. An increase in tonographic outflow facility seems to account for the IOP reduction in normal monkey eyes.

Cited by 22 publications

References 32 publications

Vasodilator Effects of Flunarizine on Retinal Blood Vessels in Anesthetized Rats

Vasodilator Effects of Flunarizine on Retinal Blood Vessels in Anesthetized Rats

The Ca2+ channel blocker flunarizine induces caspase-10-dependent apoptosis in Jurkat T-leukemia cells

Mitochondrial Dependent Apoptosis: Ameliorative Effect of Flunarizine on Ischemia–Reperfusion of Celiac Artery-Induced Gastric Lesions in the Rat

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