A Thromboxane A&lt;sub&gt;2&lt;/sub&gt;-Antagonistic Effect of Pyridinolcarbamate and Phthalazinol

Shimamoto, Takio; Takashima, Yoshimi; Kobayashi, Masahiko; Moriya, Kinya; Takahashi, Takéo

doi:10.2183/pjab1945.52.591

Cited by 23 publications

(4 citation statements)

References 6 publications

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“…In light of the pharmacological properties of phthalazinol [6,8] the increased regression of atheromatous lesions in rabbits with phthalazinol as shown in the present work may indicate that thromboxane A2 is one of the most important causative substances in progression of atheromatous lesions.…”

Section: Discussionsupporting

confidence: 54%

“…In adipocytes, thromboxane A2 is known [7] to inhibit the release of lipids by lowering cellular cyclic AMP. The rapid release of lipid droplets from foamy cells, seen in the treated animals with phthalazinol, may be due to its potent anti-thromboxane A2 activity [6] and its potent cyclic AMP phosphodiesterase-inhibiting activities [8], The adhesion of platelets is well-known to occur not only on denuded surfaces of atheromatous lesions, but also on the surface of some endo thelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a new compound, phthalazinol, was shown to have similar but much more potent pharmacological effects than pyridinolcarbamate [6]. As this agent exhibited a preventive effect on atherosclerosis in cho lesterol-fed rabbits, it was deemed necessary to determine whether or not phthalazinol would have the same effect as pyridinolcarbamate on regres sion of atheromatous lesions in atherosclerotic rabbits.…”

Section: Introductionmentioning

confidence: 99%

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Atherogenic Mechanisms: Enhancement of Regression of Atheromatous Lesions by Phthalazinol

Shimamoto¹

1978

J Vasc Res

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Atherosclerosis was produced in rabbits by feeding 1% cholesterol pellets for 15 weeks to 35 male rabbits divided into two equal groups – the placebo control and phthalazinol group – with a comparable serum cholesterol level. The phthalazinol group was given 20 mg/kg of the compound daily. 13 rabbits of both groups were on 15 weeks of the treatment and the remaining 22 rabbits were treated for 30 weeks. The treated group exhibited a statistically significant increased removal of cholesterol from atherosclerotic aortas and improvement in pathological changes. This enhancing effect was more marked in the animals treated for 30 weeks. Such evidence indicates that there are substances capable of enhancing the removal of cholesterol from atheromatous lesions. In light of the pharmacological properties of phthalazinol, the possible role of thromboxane A2 released from platelets adhered and aggregated on atheromatous plaques, in the progression of atherosclerosis is worthy of continued investigation.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Atherogenic Mechanisms: Enhancement of Regression of Atheromatous Lesions by Phthalazinol

Shimamoto¹

1978

J Vasc Res

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“…A newly synthesized compound, phthalazinol (EG 626), has been shown to have cyclic AMP phosphodiesterase inhibiting actions on arteries and platelets (1)(2)(3). Moreover, this agent also possesses highly potent, reversible and competitive antagonistic effects on throm boxane A2(TXA2) which is known to induce potent arterial contractions in which platelets participate and arterial spasm follows (4-6).…”

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Effects of Phthalazinol, Eg 626, on Membrane and Mechanical Properties of Smooth Muscle Cells of Rabbit Main Pulmonary Artery and Superior Mesenteric Artery

Suzuki

Ito

Kuriyama

et al. 1979

Japanese Journal of Pharmacology

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Abstract-Effects of phthalazinol, EG 626, on the membrane and mechanical properties of the vascular smooth muscles, namely superior mesenteric artery and main pulmonary artery of the rabbit were examined. EG 626 (10-'-3 x l0-s g/ml) did not modify the membrane potential (-56.5 nmV), length constant of the tissue (1.47 mm), and rectifying property of the membrane in the pulmonary artery. The membrane potential of the mesenteric artery (-59.8 mV) was also not modified. By treatment with 10-5 g/ml EG 626, the mechanical responses of both muscle tissues induced by either direct muscle stimulation (1 sec pulse) or by nerve stimulation (0.5 msec, 30 Hz) were suppressed. The mechanical response induced by nerve stimulation was more dominantly suppressed than that induced by direct muscle stimulation. Dose-response curve obtained from the relation between noradrenaline and mechanical response in both pulmonary and mesenteric arteries shifted to the right by treatment with 10-s g/ml EG 626. When the depolarization-contraction relationship was observed before and during application of EG 626 (10-s g/ml), using the voltage clamp technique, the application of this agent raised the mechanical threshold to evoke contraction and amplitude of the contraction evoked at any given grade of depolarization was consistently reduced as compared with that evoked in Krebs Solution. These observations suggest that EG 626 suppresses the mobilization of Ca++ during contraction and also the release of chemical transmitter from the nerve terminals by suppression of Ca++ mobilization. EG 626 would thus appear to act on the vascular smooth muscles as a vasodilator.A newly synthesized compound, phthalazinol (EG 626), has been shown to have cyclic AMP phosphodiesterase inhibiting actions on arteries and platelets (1-3). Moreover, this agent also possesses highly potent, reversible and competitive antagonistic effects on throm boxane A2(TXA2) which is known to induce potent arterial contractions in which platelets participate and arterial spasm follows (4-6).Since intracellular free Ca++ concentration is known to regulate the contraction and relaxation of muscles, investigations were carried out to determine whether or not the anti spasmic action of EG 626 on blood vessels is directly produced by relaxation of smooth muscle.To observe the effects of EG 626 on the membrane and mechanical properties of the vascular smooth muscles, the main pulmonary artery and the superior mesenteric artery of the rabbit were used.

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Preparation of 1‐[¹⁴C] hydroxymethyl‐6‐ethoxycarbonyl‐5,7‐dimethyl‐4‐phthalazone (EG‐626)

Abuki¹,

Miyazaki²

1981

Labelled Comp Radiopharmac

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A Thromboxane A<sub>2</sub>-Antagonistic Effect of Pyridinolcarbamate and Phthalazinol

Cited by 23 publications

References 6 publications

Atherogenic Mechanisms: Enhancement of Regression of Atheromatous Lesions by Phthalazinol

Atherogenic Mechanisms: Enhancement of Regression of Atheromatous Lesions by Phthalazinol

Effects of Phthalazinol, Eg 626, on Membrane and Mechanical Properties of Smooth Muscle Cells of Rabbit Main Pulmonary Artery and Superior Mesenteric Artery

Preparation of 1‐[¹⁴C] hydroxymethyl‐6‐ethoxycarbonyl‐5,7‐dimethyl‐4‐phthalazone (EG‐626)

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A Thromboxane A<sub>2</sub>-Antagonistic Effect of Pyridinolcarbamate and Phthalazinol

Cited by 23 publications

References 6 publications

Atherogenic Mechanisms: Enhancement of Regression of Atheromatous Lesions by Phthalazinol

Atherogenic Mechanisms: Enhancement of Regression of Atheromatous Lesions by Phthalazinol

Effects of Phthalazinol, Eg 626, on Membrane and Mechanical Properties of Smooth Muscle Cells of Rabbit Main Pulmonary Artery and Superior Mesenteric Artery

Preparation of 1‐[14C] hydroxymethyl‐6‐ethoxycarbonyl‐5,7‐dimethyl‐4‐phthalazone (EG‐626)

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Preparation of 1‐[¹⁴C] hydroxymethyl‐6‐ethoxycarbonyl‐5,7‐dimethyl‐4‐phthalazone (EG‐626)