Antiischemic and antiarrhythmic activities of some novel alinidine analogs in the rat heart.
The antiischemic and antiarrhythmic effects of alinidine and a number of novel alinidine analogs were examined by using perfused rat-heart models. In the isolated working rat heart, the alinidine analog TH91:21 (10 microM; a butyl derivative) significantly increased the postischemic recovery of the heart in terms of both power and efficiency when compared with the control group. In the in situ perfused heart model, this same compound, along with TH91:22 (10 microM; a pentyl derivative) also significantly reduced the severity of both ischemia- and reperfusion-induced arrhythmias in both paced and unpaced hearts. Thus this study is the first to demonstrate the potent antiarrhythmic efficacy of two novel alinidine analogs TH91:21 and TH91:22, with TH91:21 also demonstrated to be a potent antiischemic agent in the isolated working rat heart. Although the mode of action of these compounds remains unclear, results from this study suggest that it is not simply a result of bradycardia or blockade of KATP channels, two actions these compounds possess. These compounds thus possess a novel and beneficial pharmacologic profile worthy of further study.
Challinor-Rogers
J L
JL
Baker Medical Research Institute, Prahran, Victoria, Australia.
Rosenfeldt
F L
FL
Du
X J
XJ
McPherson
G A
GA
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D001919:Bradycardia / Q000188:drug therapy; D002304:Cardiac Pacing, Artificial; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects*; D008297:Male; D026902:Potassium Channel Blockers; D051381:Rats; D011921:Rats, Inbred WKY; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D013329:Structure-Activity Relationship
D000889:Anti-Arrhythmia Agents; D002317:Cardiovascular Agents; D026902:Potassium Channel Blockers; C107232:TH 91-21; C107233:TH 91-22; C022192:alinidine; D003000:Clonidine