A bradycardic agent, UL-FS 49, increases atrial force and decreases ventricular force in isolated, perfused heart preparations of dogs.

Abstract

We investigated the effects of a bradycardic agent, UL-FS 49 (1,3,4,5-tetrahydro-7,8-dimethoxy-3[3-[[2-(3,4-dimethoxyphenyl) ethyl]methylimino]propyl]-2H-3-benzazepin-2-on hydrochloride), on the sinus rate and atrial contractile force and the ventricular force in the isolated, blood-perfused right atrial and left ventricular preparations of the dog and the inhibition by UL-FS 49 of the negative cardiac responses to acetylcholine, adenosine and cromakalim. UL-FS 49 (0.003-3 mumol) decreased sinus rate, increased atrial force and decreased ventricular force in a dose-dependent manner. The threshold doses of UL-FS 49 (0.03 mumol) for atrial responses were smaller than that (1 mumol) for a ventricular response. The duration of bradycardia induced by UL-FS 49 was longer than the intropic one. Propranolol and atropine did not block the positive inotropic and negative chronotropic responses to UL-FS 49, respectively, in isolated atria. UL-FS 49 (0.1-3 mumol) dose-dependently inhibited the negative chronotropic and inotropic responses to parasympathetic nerve stimulation and acetylcholine exogenously administered. UL-FS 49 at higher doses (1 and 3 mumol) attenuated the negative inotropic but not chronotropic responses to adenosine and cromakalim.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: Y Furukawa, S Takayama, S Sawaki, Y Inoue, S Chiba
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 265 Issue 2 Pg. 801-6 (May 1993) ISSN: 0022-3565 [Print] United States
• PMID: 8496825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzazepines
• Benzopyrans
• Cardiovascular Agents
• Potassium Channels
• Pyrroles
• Cromakalim
• Adenosine
• Acetylcholine
• zatebradine

Topics

• Acetylcholine (pharmacology)
• Adenosine (pharmacology)
• Animals
• Atrial Function
• Benzazepines (pharmacology)
• Benzopyrans (pharmacology)
• Cardiovascular Agents (pharmacology)
• Cromakalim
• Dogs
• Heart Atria (drug effects)
• Heart Ventricles (drug effects)
• In Vitro Techniques
• Myocardial Contraction (drug effects)
• Perfusion
• Potassium Channels (drug effects, physiology)
• Pyrroles (pharmacology)
• Sinoatrial Node (drug effects, physiology)
• Ventricular Function