Novel quinolizidinyl derivatives as antiarrhythmic agents: 2. Further investigation.
Fifteen quinolizidine derivatives have been tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig (gp) heart tissues and to assess calcium antagonist activity. All compounds exhibited from moderate to high antiarrhythmic activity, and five of them (3, 4, 6, 13, and 15) were more active and potent than the reference drugs (amiodarone, lidocaine, procainamide, and quinidine). These compounds were studied on spontaneously beating Langendorff-perfuse gp heart; even at concentration 17-67 times higher than the corresponding EC(50) for antiarrhythmic activity, they prolonged the QT intervals only moderately, comparing favorably with amiodarone and quinidine. Compounds 3 and 15 deserve further investigation due to their interesting cardiovascular profiles.
Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. bruno.tasso@unige.it
Bruno
B
Tasso
Roberta
R
Budriesi
Iana
I
Vazzana
Pierfranco
P
Ioan
Matteo
M
Micucci
Federica
F
Novelli
Michele
M
Tonelli
Anna
A
Sparatore
Alberto
A
Chiarini
Fabio
F
Sparatore
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D054837:Quinolizidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D043585:Receptor, Muscarinic M2 / Q000502:physiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D010975:Platelet Aggregation Inhibitors; D054837:Quinolizidines; D043585:Receptor, Muscarinic M2; D014665:Vasodilator Agents