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Electrophysiological studies of 6-(N,N-diethylamino)-Hexyl-3,4,5,-Trimethoxybenzoate on ventricular muscle and
Abstract:
The agent, 6-(N,N-diethylamino)-hexyl- 3, 4, 5,-Trimethoxybenzoate (TMB-6) which relaxes smooth and skeletal muscle by interfering with intracellular Ca ++ availability was tested for its electrophysiological effects on canine cardiac Purkinje fibres and feline papillary muscles. In both tissues the drug causes a decrease in resting membrane potential and action potential amplitude as well as spontaneous rate in Purkinje fibres, and an increase in stimulus needed to reach threshold. The minimum effective dose for both tissues was similar at 7.32 x 10-5 M. The drug effects were reversible in both tissues upon removal of the TMB-6. The Ca++ -dependent action potentials of canine cardiac Purkinje fibres were also inhibited by TMB-6 at dose range of 7.32 x 10-5 -24.4 x 10-5 M. Because of its electro physiological effects of threshold, automaticity and "slow response" action potentials and its reversibility, TMB-6 could become a useful antiarrhythmic drug.
Insights
The novel agent 6-(N,N-diethylamino)-hexyl- 3, 4, 5,-Trimethoxybenzoate (TMB-6) demonstrated significant electrophysiological effects on cardiac tissues. TMB-6 shows potential as an antiarrhythmic drug due to its reversible impact on cardiac action potentials.
Area of Science:
- Cardiovascular Pharmacology
- Cardiac Electrophysiology
Background:
- Smooth and skeletal muscle relaxation is mediated by 6-(N,N-diethylamino)-hexyl- 3, 4, 5,-Trimethoxybenzoate (TMB-6) through modulation of intracellular calcium (Ca++).
- Understanding the electrophysiological effects of TMB-6 on cardiac tissue is crucial for evaluating its therapeutic potential.
Purpose of the Study:
- To investigate the electrophysiological effects of TMB-6 on canine cardiac Purkinje fibres and feline papillary muscles.
- To assess the potential of TMB-6 as an antiarrhythmic agent.
Main Methods:
- Electrophysiological recordings were performed on isolated canine cardiac Purkinje fibres and feline papillary muscles.
- The effects of varying concentrations of TMB-6 on membrane potential, action potential amplitude, and excitability were analyzed.
- Reversibility of TMB-6 effects was evaluated upon drug washout.
Main Results:
- TMB-6 decreased resting membrane potential and action potential amplitude in both cardiac tissues.
- A reduction in spontaneous rate and an increase in threshold stimulus were observed in Purkinje fibres.
- TMB-6 inhibited Ca++-dependent action potentials in a dose-dependent manner, with effects being reversible upon removal.
Conclusions:
- TMB-6 exhibits significant electrophysiological effects on cardiac Purkinje fibres and papillary muscles.
- The drug's ability to modulate threshold, automaticity, and "slow response" action potentials, coupled with its reversibility, suggests potential utility as an antiarrhythmic therapy.