Disease relevance of Fosfedil

• Effects of KB-944, a novel calcium antagonist, in several models of canine myocardial ischemia [1].
• The effects of the calcium entry blockers diltiazem, KB-944 [diethyl 4-(benzothiazol-2-yl)benzylphosphonate] and bepridil on the vulnerability of ischemically injured myocardium toward fibrillation were determined in urethane-anesthetized dogs 4 to 7 days after anterior myocardial infarction [2].
• Ambulatory monitoring and exercise testing in the evaluation of a new long-acting calcium ion antagonist KB-944 (Fostedil) for the treatment of exertional angina pectoris [3].
• One patient developed unstable angina during the treatment phase of KB-944 200 mg/day and was withdrawn [3].
• One patient developed ventricular tachycardia during treadmill testing while on KB-944 200 mg/day [3].

Psychiatry related information on Fosfedil

• Five patients complained of dyspepsia and one of headache and lethargy during KB-944 200 mg/day [3].

High impact information on Fosfedil

• Intravenous infusion of KB-944 (100 and 200 micrograms/kg/min) decreased heart rate and left ventricular systolic and aortic blood pressure [1].
• In a model of total coronary artery occlusion, KB-944 had no effect on the indirect indices of collateral function, retrograde flow and retrograde pressure [1].
• Total coronary artery blood flow and regional perfusion of normal myocardium were increased by KB-944 in both models [1].
• In papillary muscle preparations KB-944 in medium and large doses depressed force of contraction, the depressant action being greater at high rates of contraction [4].
• In atrioventricular (AV) node preparations KB-944 increased AV conduction time and in large doses produced second- or third-degree AV block only when injected into the artery supplying the AV node [4].

Biological context of Fosfedil

• Depression by KB-944 of SA nodal automaticity and AV nodal conduction occurred pari passu with coronary vasodilation, whereas force of contraction was depressed to a lesser extent in coronary vasodilator doses [4].
• The doses of KB-944 leading to a decrease in systolic blood pressure of 20% of pretreatment level were estimated to be 32.8 mg/kg in normotensive rats, 5.1 mg/kg in SHR, 6.4 mg/kg in renal hypertensive rats and 5.4 mg/kg in DOCA-NaCl hypertensive rats, respectively [5].
• Effects of a new calcium entry blocking agent, KB-944, on the membrane potential and currents of mammalian ventricular muscle cells [6].
• Neither death nor inhibition of body weight gain nor any toxic symptoms of the drug were noted in rats but an increase in water intake was found in the rats treated with over 100 mg/kg/day of KB-944 [7].
• The method consisted of mutagens or KB-944 with and without metabolic activation, and two bacteria; Salmonella typhimurium 5 test strains, TA 1535, TA 100, TA 1537, TA 1538 and TA 98, and Escherichia coli WP 2 uvr A [8].

Associations of Fosfedil with other chemical compounds

• Simultaneously, KB-944 and diltiazem decreased the heart rate, whereas papaverine increased it [9].
• The vasodilator mechanism of diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944) was investigated in anesthetized dogs and isolated aortic and taenia caecum preparations [10].

Analytical, diagnostic and therapeutic context of Fosfedil

• Thus, KB-944 maintains ischemic zone blood flow despite decreases in coronary perfusion pressure and increases in tissue flow in the collateral dependent region when aortic pressure is prevented from decreasing [1].
• Ambulatory monitoring and multistage treadmill exercise with computer-assisted electrocardiographic analysis was performed after 2 weeks of placebo therapy and after two 2-weekly periods of KB-944 therapy [3].
• The anti-anginal effects of KB-944 (Fostedil), a new calcium ion antagonist with a half life of approximately 23-28 hr, were evaluated in 20 patients with exertional angina pectoris in a placebo-controlled single-blind dose titration trial [3].
• In SHR, tolerance of KB-944 was not observed with oral administration for 5 weeks at a daily dose of 30 mg/kg [5].

References