Effect of moracizine and ethacizine on receptors of potential-operated calcium channels and calcium-binding proteins.
The action of two antiarrhytmic drugs, moracizine (MOR, CAS 31883-05-3) and ethacizine (ETHA, CAS 33414-33-4) on receptors of potential-operated CA-channels has been investigated. ETHA binding to verapamil receptors was more effective than that of MOR (IC50 = 0.53 +/- 0.08 mumol/l, respectively). The Hill coefficient for ETHA binding was similar to that of verapamil (0.64 +/- 0.09 and 0.60 +/- 0.10, respectively). Interaction of ETHA and MOR with dihydropyridine receptors in concentrations up to 10 mumol/l was similar that of verapamil, however, MOR was less potent. MOR and ETHA did not interact with calmodulin and troponin C at concentrations up to 100 mumol/l. The influence of MOR and ETHA on enzymes dependent on Ca-binding proteins (phosphodiesterase and actomyosin ATPase) was not observed up to 100 mumol/l. Comparison of clinical and electrophysiological data with these results allows the conclusion that ETHA exerts Ca-blocking effects by the interaction with verapamil receptors on potential-operated Ca-channels.
Ratner
E I
EI
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
Tkachuk
V A
VA
Baldenkov
G N
GN
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015220:Calcium Channels; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D008024:Ligands; D008564:Membrane Potentials / Q000187:drug effects; D016293:Moricizine / Q000494:pharmacology*; D010640:Phenothiazines / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D008024:Ligands; D010640:Phenothiazines; D011978:Receptors, Nicotinic; D016293:Moricizine; D014700:Verapamil; D010727:Phosphoric Diester Hydrolases; D000251:Adenosine Triphosphatases; C046818:ethacizine; D002746:Chlorpromazine