Hemorheological methods in drug research.
Development of new drugs is a sophisticated process that requires several, different methods. In our experiments we have applied two rheological models to study experimental and clinically used drugs. The antioxidant properties of several agents were estimated by erythrocyte filtration technique. The known antioxidant compound vitamin E was used to validate our measurements. An experimental cardioprotective agent, H-2545 provided significant protection against oxidative changes in red blood cell filterability (p<0.001). Although some of the examined, known cardiovascular drugs also showed significant antioxidant effect, they were less efficient than H-2545 and the scavenger effect of this novel agent exceeded the antioxidant properties of vitamin E. Modification of mexiletine with a pyrroline ring improved significantly its antioxidant capacity suggesting this molecular segment to be responsible for the antioxidant effect. In our second model the antiplatelet effect of experimental poly(ADP-ribose) polymerase (PARP) inhibitors was evaluated. Two widely used antiplatelet agents: acetyl salicylic acid and eptifibatide served as controls in the validation of the measurements. PARP inhibitors reduced ADP-induced platelet aggregation in a dose-dependent manner (p<0.05). However, their hindrance on platelet aggregation waned as the concentration of ADP rose. Regarding the platelets' role in the development of ischemic vascular diseases, the antiaggregating property of PARP inhibitors may exert additional beneficial effects on tissue blood supply under conditions of compromised vascular flow.
Marton
Zsolt
Z
1st Department of Medicine Division of Cardiology, University of Pecs Medical School, Hungary.
Halmosi
Robert
R
Alexy
Tamas
T
Horvath
Beata
B
Toth
Ambrus
A
Feher
Gergely
G
Koltai
Katalin
K
Kesmarky
Gabor
G
Habon
Tamas
T
Sumegi
Balazs
B
Hideg
Kalman
K
Toth
Kalman
K
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D000077261:Carvedilol; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D018056:Hemorheology / Q000379:methods*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology
D000975:Antioxidants; D002227:Carbazoles; D002316:Cardiotonic Agents; C441088:H 2545; D007211:Indoles; D011412:Propanolamines; D000077261:Carvedilol; D000244:Adenosine Diphosphate; D003094:Collagen; D004837:Epinephrine