General pharmacological effects of (Ethyl p-(6-guanidinohexanoyloxy)benzoate) methanesulfonate (FOY)

Okegawa, Tadao; Aishita, Hideki; Akimoto, Akira; MAKITA, Toshio; NAKAI, Hideaki; Kawasaki, Akiyoshi; Ohta, Katsumi; SHIBATA, Kuniharu; NAKAO, Yoshichika

doi:10.1254/fpj.71.71

Cited by 3 publications

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“…Thus, the relaxant action of gabexate is considered to be exerted mainly by the muscarinic receptor blocking action. The decrease in flow resistance of the sphincter of Oddi and in intestinal motility produced by gabexate (Yamasato et al 1991;Okegawa et al 1975) might also partly be due to this atropine-like action.…”

Section: Discussionmentioning

confidence: 99%

“…These protease inhibitors have a beneficial effect on acute experimental pancreatitis in rat and dog (Takasugi et al 1982;Wisner et al 1987;Wakayama et al 1989;Hirano et al 1991) and have been clinically used for pancreatitis (Takasugi & Toki 1980;Harada et al 1991). It has also been reported that gabexate reduces flow resistance of the sphincter of Oddi in dogs (Yamasato et al 1991) and inhibits intestinal motility (Okegawa et al 1975;Yamasato et al 1991). In the present experiments we have examined the possibility of muscarinic receptor blocking action of gabexate on these inhibitory effects using the guinea-pig gastric muscle.…”

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confidence: 86%

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Effects of Gabexate, a Protease Inhibitor, on Smooth Muscle of Guinea‐Pig Stomach Fundus

Hirano

Nakazawa

Tomita

1995

Pharmacology & Toxicology

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A protease inhibitor, gabexate (ethyl-p-6-guanidinohexanoyloxy benzoate), was found to have an antimuscarinic action in muscle strips of the guinea-pig gastric fundus. Gabexate reversibly inhibited carbachol-induced contractions in the presence of prostaglandin synthesis inhibitors (indomethacin or meclofenamate) with a pA2 of 5.66 for the circular and 5.25 for the longitudinal muscle. The effect was not affected by tetrodotoxin. Gabexate also inhibited contractions produced by prostaglandin E2 (PGE2) (21.7 +/- 7.3% with 30 microM, n = 12). The inhibition was markedly potentiated by anticholinesterase, diisopropyl fluorophosphate, but converted to contraction by atropine. In the absence of PGE2, gabexate produced no mechanical response on its own even after atropine application. Treatment with hemicholinium, an acetylcholine synthesis inhibitor, also converted the relaxant effect of gabexate, applied during PGE2-induced contraction, to contraction. Gabexate also inhibited contracture induced by 30 mM K+ weakly (13 +/- 2% with 30 microM, n = 5). This relaxation was abolished by atropine, without converting to contraction. PGE2 and excess K+ are likely to release acetylcholine from nerve fibres. These results suggest that the inhibitory effect of gabexate is mainly due to the muscarinic receptor blocking action. In addition, gabexate has a potentiating action on the prostaglandin-induced contraction.

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Section: Discussionmentioning

confidence: 99%

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confidence: 86%

Effects of Gabexate, a Protease Inhibitor, on Smooth Muscle of Guinea‐Pig Stomach Fundus

Hirano

Nakazawa

Tomita

1995

Pharmacology & Toxicology

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A possible approach to the suppression of side effects induced by PGE1

Nakabou

Kubota

Takada

et al. 1995

Prostaglandins, Leukotrienes and Essential Fatty Acids

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The Hypotensive Effect of Single-Dose Captopril in Diabetics

Chimori

Miyazaki

Kosaka

et al. 1986

Clinical and Experimental Hypertension. Part A: Theory and Prac

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To determine the role of the kallikrein-kinin (KK) system in patients with diabetes mellitus in relation to nephropathy and/or hypertension, the single-dose effects of captopril (25 mg, p.o.) were examined in 9 control subjects and 32 diabetics (group 1; 11 normotensives without nephropathy, group 2;10 hypertensives without nephropathy, group 3; 11 hypertensives with nephropathy). Significant hypotensive effects of captopril were found in groups 1 and 2 as well as in the control group, but not in group 3. These hypotensive effects were completely blocked by the infusion of ethyl-p-(6-guanidinohexanoyloxy) benzoate methanesulfonate (FOY), a kallikrein inhibitor. The administration of captopril during vehicle infusion induced a significant elevation of plasma renin activity (PRA) at 60 and 120 min after captopril in each group, except for group 3. FOY cancelled these captopril-induced effects on PRA in those groups. No correlation was found between pretreatment PRA and the changes in mean blood pressure (MBP) after captopril during vehicle infusion in whole diabetics. In addition, the daily urinary excretion of kallikrein in group 3 was significantly lower than that in groups 1 and 2 as well as in the control group. These results suggest that the hypotensive action of captopril in diabetics without nephropathy may be largely due to activating the KK system, and that the KK system may be suppressed in hypertensive diabetics with nephropathy.

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General pharmacological effects of (Ethyl p-(6-guanidinohexanoyloxy)benzoate) methanesulfonate (FOY)

Cited by 3 publications

References 0 publications

Effects of Gabexate, a Protease Inhibitor, on Smooth Muscle of Guinea‐Pig Stomach Fundus

Effects of Gabexate, a Protease Inhibitor, on Smooth Muscle of Guinea‐Pig Stomach Fundus

A possible approach to the suppression of side effects induced by PGE1

The Hypotensive Effect of Single-Dose Captopril in Diabetics

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