Angina pectoris: Effects of lidoflazine on exercise tolerance and chest pain

Jenkins, Michael; Swallow, Edith A.; Abdel-Hadi, Omar; Kidner, P. H.

doi:10.1016/0002-9149(81)90583-x

Cited by 15 publications

(4 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the early 1990s questions on the safety of CCBs raised when lidoflazine that had been considered as a very promising therapeutic agent (Jenkins et al, 1981) was withdrawn after publication that its effects were both beneficial and detrimental. The main observation reported is summarized in the following sentences: “During the randomized, placebo-controlled phase of the study with 7-week treatment periods, 9 of 11 patients who completed this phase of the study preferred lidoflazine and all demonstrated improved exercise capacity with lidoflazine compared to placebo.…”

Section: Key Information About Clinical Usefulness Of Ccbsmentioning

confidence: 99%

Discovery and Development of Calcium Channel Blockers

2017

View full text Add to dashboard Cite

In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan) and Heibrunn (USA) experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB) of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are important factors of their action. The high sensitivity of hypertensive animals is explained by the partial depolarization of their arteries. It is noted that they are arteriolar dilators and that they cannot be simply considered as vasodilators. The second part of this report provides key information about clinical usefulness of CCBs. A section is devoted to the controversy on their safety closed by the Allhat trial (2002). Sections are dedicated to their effect in cardiac ischemia, in cardiac arrhythmias, in atherosclerosis, in hypertension, and its complications. CCBs appear as the most commonly used for the treatment of cardiovascular diseases. As far as hypertension is concerned, globally the prevalence in adults aged 25 years and over was around 40% in 2008. Usefulness of CCBs is discussed on the basis of large clinical trials. At therapeutic dosage, they reduce the elevated blood pressure of hypertensive patients but don't change blood pressure of normotensive subjects, as was observed in animals. Those active on both L- and T-type channels are efficient in nephropat...

show abstract

Section: Key Information About Clinical Usefulness Of Ccbsmentioning

confidence: 99%

Discovery and Development of Calcium Channel Blockers

2017

View full text Add to dashboard Cite

show abstract

“…Lidoflazine is specifically indicated in the treatment of patients with chronic stable angina (3,11,12,16,20,21,30,35,36,40,47,51,56,57).…”

Section: Clinical Usementioning

confidence: 99%

“…l), a derivative of piperazine which belongs to the chemically heterogeneous group of the Ca2+ entry blockers (66,67), has been repeatedly shown to improve quality of life and myocardial performance in patients with ischemic heart disease (3,11,12,16,(20)(21)(22)30,35,36,40,47,51,56,57). The hemodynamic properties of lidoflazine, as observed in patients with angina pectoris, suggest that chronic treatment with the drug is particularly effective in curtailing the deleterious effect of overload in the diseased myocardium.…”

mentioning

confidence: 99%

Lidoflazine

Vanhoutte

Nueten

1983

Cardiovascular Drug Reviews

View full text Add to dashboard Cite

“…The drug is in clinical use as an oral antianginal agent (Jenkins et al 1981;Keulen 1973;Strauss 1984). When administered intravenously in a dose of 1.0 mg/kg over 10 minutes it has been found to protect the myocardium functionally, biochemically and structurally from ischaemic damage during open heart surgery using the intermittent crossclamping technique (Flammeng et al 1983).…”

mentioning

confidence: 99%

Intravenous Lidoflazine in Healthy Volunteers

et al. 1991

View full text Add to dashboard Cite

Haemodynamic effects of a IO-minute intravenous infusion of lidoflazine (0.5 and 1.0 mg/ kg at 2 different times) were studied in 7 healthy male volunteers (age 22 to 30 years). Blood pressure, 12-lead ECG impedance plethysmography of right lower leg and M-mode echocardiography were recorded before and up to 5 hours after infusion. Mean values for heart rate, blood pressure, lower leg blood flow and lower leg vascular resistance did not change significantly after infusion, but I volunteer showed bradycardia. No arrhythmias were observed. All ECG recordings displayed repolarisation changes (ST-T depression, afterpotential) throughout the study. The frequency-corrected QT duration was prolonged. Electromechanical systole, measured as the time from the Q wave to the most anterior point of the left ventricular wall endocardium during systole did not change. Mean and maximum rapid diastolic movement of the posterior wall increased, indicating improved diastolic filling. Systolic wall velocity and also fractional shortening and the ejection fraction decreased temporarily (30 to 60 minutes) after 1.0 mgjkg of lidoflazine. It is concluded that intravenously administered lidoflazine, like other calcium antagonists, improves diastolic cardiac relaxation and at 1.0 mgjkg also reduces systolic contractions. In contrast to other calcium antagonists, however, lidoflazine appears not to cause peripheral vasodilation. Further investigation of possible arrhythmogenic effects in myocardial ischaemia is warranted.

show abstract

Angina pectoris: Effects of lidoflazine on exercise tolerance and chest pain

Cited by 15 publications

References 15 publications

Discovery and Development of Calcium Channel Blockers

Discovery and Development of Calcium Channel Blockers

Lidoflazine

Intravenous Lidoflazine in Healthy Volunteers

Contact Info

Product

Resources

About