Electrocardiographic and electrophysiologic effects of pirmenol in ventricular tachycardia

Estes, N.A. Mark; Gold, R; Cameron, James; Haffajee, Charles I.; Marshall, Melanie; Mack, Keith; Salem, Deeb N.

doi:10.1016/0002-9149(87)90140-8

Cited by 7 publications

(2 citation statements)

References 14 publications

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“…The dual effects of pirmenol on action potential duration observed in the present study show similarities with results from a previous study on the same preparation (Nakaya et al, 1988), namely 3 and 1OpM pirmenol prolonged and 100 M pirmenol shortened the action potential duration significantly. At clinically used concentrations, 7.3 to 9.1 ,M for intravenous administration (Estes et al, 1987;Nieminen et al, 1987) and 4.7 to 7.7 for oral administration (Farnham, 1987;Estes et al, 1987), pirmenol seems to show the ability to prolong action potentials. The characteristics of the use-dependent inhibition of V,,.x induced by pirmenol are similar to those of slow kinetic drugs, such as disopyramide which was shown to have a recovery time constant of 12.0 to 37.8s (Campbell, 1983a;Varro et al, 1985), rather than of fast kinetic drugs, according to the classification proposed by Courtney (1980a).…”

Section: Recoveryfrom the Use-dependent Effect Ofpirmenolmentioning

confidence: 96%

“…Pirmenol, cis-( ± )-a-[3-(2,6-dimethyl-1-piperidinyl)propyl]-aphenyl-2-pyridinemethanol monohydrochloride, is a new antiarrhythmic agent which has been studied in cardiac muscle in vitro (Reder et al, 1980;Dukes et al, 1986;Nakaya et al, 1988). Furthermore, pirmenol has already undergone some experimental Steffe et al, 1980;Mertz & Kaplan, 1982;Lynch et al, 1986;Hashimoto et al, 1988) as well as clinical studies to assess its antiarrhythmic potential in vivo (Chang, 1987;Estes et al, 1987;Farnham, 1987;Nieminen et al, 1987). Pharmacological studies have indicated that pirmenol is a class I antiarrhythmic drug (Reder et al, 1980;Nakaya et al, 1988) and resembles disopyramide (Dukes et al, 1986) in its electrophysiological effects on the maximum rate of rise of the action potential (V,,.x) and the action potential duration of the myocardium.…”

Section: Introductionmentioning

confidence: 99%

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Use‐dependent effects of pirmenol on and conduction in guinea‐pig ventricular myocardium

Hasegawa

Hirai

Noguchi

et al. 1990

British J Pharmacology

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1 The use-dependent effects of pirmenol, a new antiarrhythmic drug, on the maximal rate of rise (V,) of the action potential, conduction velocity, and their corresponding recovery kinetics were studied in isolated papillary muscles of guinea-pig. Standard microelectrode techniques were used to monitor the conduction and action potential characteristics of the muscles. 2 Pirmenol decreased V,,,x and the overshoot of action potentials in a dose-dependent fashion. Also, doses of pirmenol greater than 1 mm abolished the generation of action potentials. Low concentrations of pirmenol (3 and 1OpM) prolonged the action potential duration, while concentrations greater than 0.1 mm shortened it markedly.3 The resting block of V,,.x in the presence of 10 and 30M pirmenol was 9.48 + 3.12 and 20.36 + 3.61%, and that of conduction velocity 2.87 + 1.52 and 6.58 + 2.09%, respectively. 4 The degree of use-dependent block induced by 10 and 30M pirmenol during 0.2, 1, 2 and 3Hz stimulations was dose-and rate-dependent. 5 In the presence of 30Mm pirmenol, mean values of time constants for the onset of the use-dependent inhibition of V,,,x and conduction velocity during a 2Hz stimulation were 1.32 + 0.15 and 1.28 + 0.09s, respectively. The recovery time constants averaged 15.83 + 2.14 (for V,,.x) and 27.80 + 8.74 (for conduction velocity) s in the presence of 30 gM pirmenol.6 These results showed that the characteristics of the use-dependent inhibition of V,,mx and conduction velocity induced by pirmenol are similar to those of slow kinetic drugs such as disopyramide rather than of fast ones.

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Section: Recoveryfrom the Use-dependent Effect Ofpirmenolmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Use‐dependent effects of pirmenol on and conduction in guinea‐pig ventricular myocardium

Hasegawa

Hirai

Noguchi

et al. 1990

British J Pharmacology

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Pirmenol: An antiarrhythmic drug with unique electrocardiographic features—a double‐blind placebo‐controlled comparison with quinidine

Salerno

Fifield

Farmer

et al. 1991

Clinical Cardiology

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Summary:Previous reports have stated that pirmenol is a Class IA antiarrhythmic drug that prolongs the QT interval, but did not use computerized electrocardiography. We randomized 18 patients with frequent ventricular ectopic depolarizations to pirmenol (8 patients) or quinidine (10 paticnts). Pirmenol was effective and tolerated for suppression of arrhythmia in all 7 patients treated (1 patient withdrew for personal reasons) but quinidine was effective and tolerated for 4 weeks in only 5 of 10 patients (p < 0 .OS) . Using computerized 12-lead electrocardiography. the mean change in PR interval from placebo to treatment was 5 & 18 ms for quinidine and 5 & 1 1 ms for pirmenol (p=NS). The mean change in QRS interval was 5 + 14 ms for quinidine and 10+5 ms for pirmenol (p=NS). The mean change in QT interval was 4 6 k 3 0 ms tor quinidine and 8+9 ms for pirmenol (p <0.01) and the mean change in JT interval was 41 _+36 ms for quinidine and -2+ 10 ms for pirmenol (p

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Pharmacokinetics of pirmenol in young and elderly subjects

Ferry

Campbell

Bland

et al. 1992

Eur J Clin Pharmacol

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The steady state pharmacokinetics of pirmenol was compared in twelve healthy young (aged 18 to 45 y) and 11 elderly subjects (over 65 y) subjects given pirmenol HCl 100 mg every 12 h for a total of 14 doses. In addition, the single-dose pharmacokinetics of pirmenol was determined following a 100 mg oral dose in the young subject group for comparison with the results of repeated administration. In the young subjects, the mean single-dose and steady-state CLR of pirmenol were similar; however, Ae was 29% higher and CL/f was 22% lower at steady state than after the single dose. Steady-state (fourteenth dose) Cmin, Cmax, tmax, lambda z, Ae, CL/f, CLR and V values were similar in the young and elderly subjects. Based on pharmacokinetic considerations, the dosage of pirmenol is unlikely to differ in young and elderly subjects.

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Electrocardiographic and electrophysiologic effects of pirmenol in ventricular tachycardia

Cited by 7 publications

References 14 publications

Use‐dependent effects of pirmenol on and conduction in guinea‐pig ventricular myocardium

Use‐dependent effects of pirmenol on and conduction in guinea‐pig ventricular myocardium

Pirmenol: An antiarrhythmic drug with unique electrocardiographic features—a double‐blind placebo‐controlled comparison with quinidine

Pharmacokinetics of pirmenol in young and elderly subjects

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