Paper Information

Title: 

INOTROPIC AND CHRONOTROPIC EFFECTS OF METHYL CARBOSTIRYL (MC) DERIVATIVES IN ISOLATED RAT ATRIA

Type: POSTER
Author(s): HOSSEINI AZAR,SHAFIEINIK R.*,PARSAEI H.,SADEGHIAN HAMID
 
 *DEPARTMENT OF PHARMACOLOGY, SCHOOL OF MEDICINE, PHARMACOLOGICAL RESEARCH CENTER OF MEDICINAL PLANTS, MASHHAD UNIVERSITY OF MEDICAL SCIENCES, MASHHAD, IRAN
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2009Volume 19
 
 
Abstract: 

In cardiac, selective phosphodiesterase 3 inhibitors (PDE3Is) increase contractility force. At the present time, some of selective pde3is (e.g. amrinone, milrinone and cilostazol) have been approved for the treatment of congestive heart failure (CHF). Comparing to cardiac glycosides, they have wider therapeutic windows and do not have arrhythmia side effect. In this research, we evaluated the potential cardiotonic activity of new synthetised selective PDE3 inhibitors (mc1, 2, 3, 4, 7, 8, 12) using the spontaneously beating atria model. In each experiment, atrium of reserpine-treated rat was isolated and the contractile and chronotropic effects of a synthetized compounds were assessed. The results showed that among new compounds the best pharmacological profile was obtained with the compound mc2, which displayed selectivity for increasing the force of contraction (155.6±12% change over the control ) but the positive chronotropic effect of isoprenaline was not affected by mc2 (106±5.6% change over the control). The EC50 of isoprenaline 28.5±4 in theabsence, 15.8±12.7 in the presence of 100μm of mc2. In conclusion, this studyprovides functional evidence for the positive inotropic effect of compounds. Considering the augmentation of isoprenaline positive inotropic concentration-response with mc2, we conclude that mc2 produces its effect via potentiation of cAMP-dependent signaling system and possibly by inhibition of PDE3 activity.

 
Keyword(s): INOTROPIC AND CHRONOTROPIC EFFECTS, METHYL CARBOSTIRYL (MC) DERIVATIVES, PDE3I
 
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