Anti-thrombotic effect of KC-404, a novel cerebral vasodilator

Ohashi, Mitsuo; Kudo, Yoshitaka; Ichikawa, Yoshimitsu; Nishino, Koichiro

doi:10.1016/0306-3623(86)90179-5

Cited by 12 publications

(6 citation statements)

References 17 publications

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“…Ibudilast has a beneficial effect on ischaemia/reperfusion‐induced brain dysfunction ( Ohashi et al ., 1986a , 1986b ; Yanase et al ., 1996 ). In addition, previous in vitro studies show that ibudilast has a protective effect against exitotoxicity in cultured oligodendorocytes ( Yoshioka et al ., 1998 ; 2000 ), neurons ( Tominaga et al ., 1996 ) and hippocampal slices ( Yanase et al ., 1996 ).…”

Section: Discussionmentioning

confidence: 99%

“…3‐Isobutyryl‐2‐isopropylpyrazolo[1,5‐a]pyridine (ibudilast) has vasodilating, anti‐platelet and anti‐leukotriene effects ( Fukuyama et al ., 1993 ; Kawasaki et al ., 1992 ; Ohashi et al ., 1986a , 1986b ), and it is widely used in Japan for bronchial asthma and cerebrovascular disorders. Previous in vitro studies showing that ibudilast prevents exicitotoxicity in cultured oligodendroglial cells ( Yoshioka et al ., 1998 ; 2000 ) and neurons ( Tominaga et al ., 1996 ) may support the effectiveness of ibudilast in cerebrovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

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Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model

Takuma

Lee

Enomoto

et al. 2001

British J Pharmacology

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1 We examined the eect of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (ibudilast), which has been clinically used for bronchial asthma and cerebrovascular disorders, on cell viability induced in a model of reperfusion injury. 2 Ibudilast at 10 ± 100 mM signi®cantly attenuated the H 2 O 2 -induced decrease in cell viability. 3 Ibudilast inhibited the H 2 O 2 -induced cytochrome c release, caspase-3 activation, DNA ladder formation and nuclear condensation, suggesting its anti-apoptotic eect. 4 Phosphodiesterase inhibitors such as theophylline, pentoxyfylline, vinpocetine, dipyridamole and zaprinast, which increased the guanosine-3',5'-cyclic monophosphate (cyclic GMP) level, and dibutyryl cyclic GMP attenuated the H 2 O 2 -induced injury in astrocytes. 5 Ibudilast increased the cyclic GMP level in astrocytes. 6 The cyclic GMP-dependent protein kinase inhibitor KT5823 blocked the protective eects of ibudilast and dipyridamole on the H 2 O 2 -induced decrease in cell viability, while the cyclic AMPdependent protein kinase inhibitor KT5720, the cyclic AMP antagonist Rp-cyclic AMPS, the mitogen-activated protein/extracellular signal-regulated kinase inhibitor PD98059 and the leukotriene D 4 antagonist LY 171883 did not. 7 KT5823 also blocked the eect of ibudilast on the H 2 O 2 -induced cytochrome c release and caspase-3-like protease activation. 8 These ®ndings suggest that ibudilast prevents the H 2 O 2 -induced delayed apoptosis of astrocytes via a cyclic GMP, but not cyclic AMP, signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model

Takuma

Lee

Enomoto

et al. 2001

British J Pharmacology

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“…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%

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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“…Ibudilast is used clinically to treat bronchial asthma and cerebrovascular disorders. These clinical uses are based on the ability of ibudilast to inhibit platelet aggregation (Kishi et al, 2001), improve cerebral blood fl ow (Kishi et al, 2001;Ohashi et al 1986) and attenuate allergic reactions (Kishi et al, 2001;Fukuyama et al, 1993;Nishino et al, 1983Nishino et al, , 1984.…”

Section: Introductionmentioning

confidence: 99%

Determination of ibudilast in human serum by high‐performance liquid chromatography for pharmacokinetic study

Yoon

Cho²,

Lee

2009

Biomedical Chromatography

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A simple, accurate, precise and cost effective reversed-phase HPLC method was developed to determine the concentration of ibudilast in human serum. Ibudilast and an internal standard, butyl 4-hydroxybenzoate, were extracted by liquid-liquid extraction with methyl tert-butyl ether. HPLC analysis was carried out under the following conditions: a Luna C(18)(2) 5 microm column, a mobile phase of acetonitrile-0.02% phosphoric acid (50 : 50, v/v, adjusted to pH 6.0 with triethylamine) and a UV detector at 319 nm. The chromatograms showed good resolution and sensitivity as well as no interference from the human serum. The calibration curves were linear over the concentration range, 1-100 ng/mL, for serum with correlation coefficients >0.999. The intra- and inter-day assay precision as well as the accuracy fulfilled the international requirements. The mean absolute recovery for human serum was 101.7 +/- 6.1%. The lower limit of quantitation in human serum was 1 ng/mL, which is sensitive enough for pharmacokinetic studies. Stability studies revealed that ibudilast in human serum was stable during storage as well as during the assay procedure. This method was applied successfully to an examination of the pharmacokinetics of ibudilast in human subjects following a single oral dose of an ibudilast (10 mg) capsule.

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Anti-thrombotic effect of KC-404, a novel cerebral vasodilator

Cited by 12 publications

References 17 publications

Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model

Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model

Ibudilast May Improve Retinal Circulation in Patients with Diabetes mellitus

Determination of ibudilast in human serum by high‐performance liquid chromatography for pharmacokinetic study

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