Cardiovascular effects of KUR-1246, a new tetrahydronaphthalen derivative beta2-adrenoceptor agonist and a selective uterine relaxant.
The aim of this study was to assess the cardiovascular effects of KUR-1246 (CAS 194785-31-4, (-)-bis(2-{[(2S)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl) phenyl] ethyl}amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy}-N,N-dimethylacetamide)monosulfate), a new beta2-adrenoceptor agonist tocolytic agent. In conscious dogs, the intravenous administration of KUR-1246 at 0.1 and 1 microg/kg had no effects on blood pressure, heart rate or femoral artery blood flow. KUR-1246 at 10 and 100 microg/kg significantly decreased blood pressure and increased heart rate. In the electrocardiograms, KUR-1246 did not affect QT intervals or QTc. In addition, the cardiac effects of KUR-1246 were evaluated in in vitro electrophysiological studies. KUR-1246 at 10 micromol/L did not affect action potential parameters (the maximal upstroke velocity, resting membrane potential, action potential amplitude and action potential durations) in isolated papillary muscles of guinea pigs or in the human ether-a-go-go related gene (HERG) tail current recorded from stably transfected human embryonic kidney (HEK) 293 cells. On the basis of these results, the effects of KUR-1246 in conscious dogs on the cardiovascular system appear to be limited to changes in blood pressure and heart rate. Therefore, KUR-1246 is unlikely to provoke ventricular arrhythmias by delaying the ventricular repolarization.
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo Japan.
Yoshio
Y
Furihata
Yoshiyuki
Y
Motokawa
Satoshi
S
Murata
Sumiyoshi
S
Kiguchi
Mamoru
M
Kobayashi
Makoto
M
Murakami
Masami
M
Kojima
Toshinori
T
Yamamoto
D000081:Acetamides / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D058647:Adrenergic alpha-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents; D002460:Cell Line; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects
D000081:Acetamides; D058647:Adrenergic alpha-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D002317:Cardiovascular Agents; D051638:Ether-A-Go-Go Potassium Channels; D009281:Naphthalenes; C425888:bedoradrine