Cardiovascular effects of R- and S-enantiomers of Ro 22-9194, (2R)-2-amino-N- (2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate and (2S)-2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide L-tartrate, in dog heart preparations.
A newly synthesized compound, Ro 22-9194, relates in part of to the chemical structure of lidocaine. The cardiac effects of R- and S-enantiomers of Ro 22-9194 were investigated on isolated right atrial and left ventricular (LV) preparations which were cross-perfused with blood from another donor dog and an anesthetized open-chest dog. Each enantiomer (1-1,000 micrograms) decreased dose-dependently the sinus rate and atrial developed tension in the isolated right atrium (RA). The negative chronotropic responses to R- and S-enantiomers were not significantly different, and the negative inotropic responses to R- and S-enantiomers were also generally comparable. Both R- and S-enantiomers (10-3,000 micrograms) also decreased the ventricular developed tension in a dose-related manner similarly. In neurally decentralized, anesthetized, open-chest dogs, R- and S-enantiomers (0.1-3 mg/kg) injected into the femoral vein dose-dependently prolonged atrioventricular (A-V) conduction time and decreased heart rate (HR) and arterial blood pressure (ABP). Each enantiomer (3 mg/kg intravenously, i.v.) prolonged the interval between His bundle and ventricle rather than the interval between atrium and His bundle. There was no significant difference between R- and S-enantiomer-induced negative dromotropic actions. The duration of the negative dromotropic response to each enantiomer (3 mg/kg i.v.) was longer than that of the decrease in BP. These results suggest that the negative chronotropic, inotropic, and dromotropic effects of R- and S-enantiomers of Ro 22-9194 are not stereospecific in dog heart.
Murakami
M
M
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Karasawa
Y
Y
Ren
L M
LM
Takei
M
M
Narita
M
M
Chiba
S
S
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects; D013237:Stereoisomerism
D011725:Pyridines; C066993:Ro 22-9194