[Correlation between the antiarrhythmic activity of acyl derivatives of phenothiazine and their affinity for phospholipid membranes].
The interaction of thirteen antiarrhythmic active phenothiazine 10-acylaminopropionil derivatives with artificial phospholipid membranes was studied. Blinding constant (K) of this interaction was determined by means of a fluorescent probe. There was found a valid correlation between K and antiarrhythmic activity (A) for 10 substances; the greater the K--the greater the A. Three substances characterized by the greatest K had, however, a low A. It can be assumed that the interaction of antiarrhythmic drugs with phospholipids of target membranes in vivo is an important element of the molecular mechanism of action. At the same time a very high affinity to lipids can possibly cause a delocalization of the drug in the organism and a decrease of its antiarrhythmic activity.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D008563:Membrane Lipids; D008567:Membranes, Artificial; D010640:Phenothiazines / Q000627:therapeutic use; D010743:Phospholipids
D000889:Anti-Arrhythmia Agents; D008563:Membrane Lipids; D008567:Membranes, Artificial; D010640:Phenothiazines; D010743:Phospholipids
Korreliatsiia mezhdu antiaritmicheskoĭ aktivnost'iu atsil'nykh proizvodnykh fenotiazina i ikh srodstvom k fosfolipidnym membranam.