Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. 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. The mean (+/- SEM) exercise time to the development of angina on treadmill walking increased from 6.9 +/- 0.4 min on placebo to 9.4 +/- 0.5 min on KB-944 100 mg/day (P less than 0.001) and 9.7 +/- 0.8 min on KB-944 200 mg/day (P less than 0.001 vs placebo and not significant vs KB-944 100 mg/day). The time to the development of 1 mm ST-segment depression of 5.3 +/- 0.4 min on placebo increased to 6.5 +/- 0.5 and 6.6 +/- 0.5 min on KB-944 100 and 200 mg/day, respectively (P less than 0.01 vs placebo). The heart rate at rest of 77 +/- 3 beats/min on placebo was reduced to 68 +/- 3 beats/min on KB-944 100 mg/day (P less than 0.001) and 71 +/- 2 beats/min on KB-944 200 mg/day (P less than 0.01). The maximal heart rate and the rate-pressure product were not altered by KB-944 therapy. One patient developed unstable angina during the treatment phase of KB-944 200 mg/day and was withdrawn. Five patients complained of dyspepsia and one of headache and lethargy during KB-944 200 mg/day. One patient developed ventricular tachycardia during treadmill testing while on KB-944 200 mg/day. The 24-hr ambulatory monitoring data confirmed the findings of exercise testing. KB-944 (Fostedil) in a dose of 100 mg once daily was well tolerated as compared to KB-944 200 mg once daily and both the doses were equally effective. The drug merits further evaluation for the treatment of exertional angina pectoris.
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PMID: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. 390 75

The cardiac electrophysiologic actions of a novel calcium antagonist, KB-944 [Fostedil, Abbott-53986, diethyl 4-(benzothiazol-2-yl) benzylphosphonate], were examined in anesthetized dogs. Cumulative doses of 0.5, 2.5 and 12.5 mg/kg i.v. produced dose-dependent increases in atrioventricular (AV) nodal refractoriness and conduction time (AH interval), although failing to alter atrial or ventricular refractoriness. Intra-atrial, infranodal and intraventricular conduction (PA, HV and H-EG intervals, respectively) were unchanged. In three of nine dogs, 2.5 to 12.5 mg/kg of KB-944 produced third degree AV blockade. Pretreatment with propranolol (0.1 mg/kg) was accompanied by sinoatrial blockade in three of five dogs who later received 12.5 mg/kg of KB-944. Glucagon (4 micrograms/kg) reversed the electrophysiologic changes associated with administration of KB-944 alone or in conjunction with propranolol. An examination of the temporal profiles of the cardiac electrophysiologic effects of KB-944 indicated selective alterations in AV nodal conduction and refractoriness for durations of approximately 60, 120 and 180 to 240 min after administration of 0.3, 1.0 or 3.0 mg/kg i.v. These results suggest that KB-944 may be an effective agent for treatment of supraventricular tachyarrhythmias via selective depression of the AV nodal conduction system.
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PMID:Cardiac electrophysiologic actions of KB-944 (Fostedil), a new calcium antagonist, in the anesthetized dog. 654 Aug 6