Influence of indomethacin on an increase in cerebral blood flow induced by KC-404, a novel cerebral vasodilator, in an anesthetized dog

Kudo, Yoshitaka; Sugiura, Hiroyuki; Ohashi, Mitsuo; Nishino, Koichiro

doi:10.1016/0306-3623(86)90050-9

Cited by 3 publications

(5 citation statements)

References 9 publications

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“…First, ibu dilast vasodilates the carotid artery system in vivo [2,4] and relaxes the cerebral vessels [5,6], and acts specifically on the terminal ves sels like brain [3,4,6,8], The drug thus may similarly be effective on the retinal vessels of the internal carotid artery system. Second, ibudilast suppresses platelet aggregation [4.…”

Section: Discussionmentioning

confidence: 99%

“…The chemical structure is shown in figure 1. This vasodilator selectively increases verte bral blood flow when compared with femoral blood flow in vivo [2,4] and in vitro [5,6], It increases regional cerebral blood flow in cats, and also enhances cerebral venous output, oxygen and glucose consumption in the brain of anesthetized dogs [4], The drug indirectly relaxes the smooth muscle of the internal carotid artery and cerebral vessels [7,8], through a mechanism linked to PGI?, a va sodilating cyclooxygenase metabolite. Thus the drug improves brain circulation without reducing blood pressure [2], Ibudilast is also known to increase prostacyclin which sup presses platelet aggregation [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Ibudilast May Improve Retinal Circulation in Patients with Diabetes mellitus

Suzuki¹,

Sugihara²,

Ishibashi³

et al. 1992

Ophthalmic Res

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Ibudilast selectively vasodilates cerebral vessels without reducing blood pressure. We investigated the effect of the drug on retinal circulation in 8 patients with diabetes mellitus, using the video-densitometric image analysis of fluorescein angiography. We compared the build up time, the time constant of washout rate and the mean circulation time (MCT) before and after oral therapy with ibudilast. After 2 weeks of daily administration (30 mg), MCT was shortened significantly (4.2 ± 2.8 vs. 3.0 ± 1.6 s, p = 0.0215). Since retinal circulation in patients with diabetes mellitus was improved by ibudilast, the drug may be useful to treat disorders such as diabetic retinopathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ibudilast May Improve Retinal Circulation in Patients with Diabetes mellitus

Suzuki¹,

Sugihara²,

Ishibashi³

et al. 1992

Ophthalmic Res

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“…Ibudilast attenuated the production of proinflammatory mediators and cytokines including superoxide, tumor necrosis factor (TNFa), interferon (IFN)-g and interleukin-6 (Niwa et al, 1995;Mizuno et al, 2004;Feng et al, 2004). In addition, ibudilast selectively increased vertebral and internal carotid blood flow without significantly affecting the systemic blood pressure and cardiac frequency of anesthetized dogs (Kudo et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Preferential inhibition of human phosphodiesterase 4 by ibudilast

et al. 2006

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“…The clinical uses are based on the ability of ibudilast to relax airway smooth muscle, 13) attenuate allergic reaction, [13][14][15][16] inhibit the aggregation of platelets, 15,16) and increase cerebral blood flow [17][18][19][20] mainly through inhibition of phosphodiesterases (PDEs). 21,22) A previous study demonstrated that 2-week administration of ibudilast shortened the mean retinal circulation time in patients with diabetes mellitus.…”

mentioning

confidence: 99%

“…In addition, we sought to determine whether the retinal vascular responses to ibudilast are mediated by a mechanism that involves prostanoids, since the contribution of the cyclooxygenase (COX) pathway to ibudilast-induced vasodilation of cerebral blood vessels is strongly suggested. 17,18) For this purpose, we examined effects of indomethacin, a nonselective inhibitor of COX, on the retinal vascular responses to ibudilast.…”

mentioning

confidence: 99%

Vasodilator Effects of Ibudilast on Retinal Blood Vessels in Anesthetized Rats

Noguchi

Mori

Sakamoto

et al. 2009

Biological & Pharmaceutical Bulletin

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Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a a]pyridine) is clinically used as a cerebral vasodilator in Japan. However, the effects of ibudilast on retinal blood vessels have not been fully examined. The aim of this study, therefore, was to examine the effects of ibudilast on retinal blood vessels in rats in vivo. Male Wistar rats (8 to 10 weeks old) were anesthetized with thiobutabarbital (120 mg/kg, intraperitoneally (i.p.)). Retinal vascular images were captured with a fundus camera system for small animals, and the diameter of retinal blood vessels was measured. Ibudilast (0. 1 and 1 mg/kg, intravenously (i.v.)) elicited a sustained increase in the diameter of retinal blood vessels and heart rate without altering systemic blood pressure. The effects of ibudilast were significantly reduced by treatment with the nonselective cyclooxygenase inhibitor indomethacin (5 mg/kg, i.p.). These results suggest that ibudilast dilates retinal blood vessels through cyclooxygenase-dependent mechanisms in rats in vivo.

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Influence of indomethacin on an increase in cerebral blood flow induced by KC-404, a novel cerebral vasodilator, in an anesthetized dog

Cited by 3 publications

References 9 publications

Ibudilast May Improve Retinal Circulation in Patients with Diabetes mellitus

Ibudilast May Improve Retinal Circulation in Patients with Diabetes mellitus

Preferential inhibition of human phosphodiesterase 4 by ibudilast

Vasodilator Effects of Ibudilast on Retinal Blood Vessels in Anesthetized Rats

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