Document Detail

Use-dependent effects of pirmenol on Vmax and conduction in guinea-pig ventricular myocardium.
MedLine Citation:
PMID:  2361175     Owner:  NLM     Status:  MEDLINE    
1. The use-dependent effects of pirmenol, a new antiarrhythmic drug, on the maximal rate of rise (Vmax) 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 Vmax 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 10 microM) prolonged the action potential duration, while concentrations greater than 0.1 mM shortened it markedly. 3. The resting block of Vmax in the presence of 10 and 30 microM 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 30 microM pirmenol during 0.2, 1, 2 and 3 Hz stimulations was dose- and rate-dependent. 5. In the presence of 30 microM pirmenol, mean values of time constants for the onset of the use-dependent inhibition of Vmax and conduction velocity during a 2 Hz stimulation were 1.32 +/- 0.15 and 1.28 +/- 0.09 s, respectively. The recovery time constants averaged 15.83 +/- 2.14 (for Vmax) and 27.80 +/- 8.74 (for conduction velocity) s in the presence of 30 microM pirmenol. 6. These results showed that the characteristics of the use-dependent inhibition of Vmax and conduction velocity induced by pirmenol are similar to those of slow kinetic drugs such as disopyramide rather than of fast ones.
J Hasegawa; S Hirai; N Noguchi; I Hisatome; H Kotake; H Mashiba
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  99     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1990 Apr 
Date Detail:
Created Date:  1990-08-08     Completed Date:  1990-08-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  815-9     Citation Subset:  IM    
Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
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MeSH Terms
Action Potentials / drug effects
Anti-Arrhythmia Agents / pharmacology*
Guinea Pigs
Heart Conduction System / drug effects*
Heart Ventricles / drug effects
Membrane Potentials / drug effects
Papillary Muscles / drug effects
Piperidines / pharmacology*
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Piperidines; 61477-94-9/pirmenol

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