Investigations on the pharmacology of the cardioprotective guanidine ME10092

Journal of Cardiovascular Pharmacology
M DambrovaJ E S Wikberg

Abstract

The guanidine compound ME10092 (1-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine), which possesses a strong cardioprotective effect to ischemia-reperfusion, was assessed for different pharmacological actions that may underlie its cardioprotective effect. In the living rat ME10092 decreased the blood pressure and heart rate in a dose-dependent manner. We found ME10092 to bind to alpha 1- and alpha 2-adrenoreceptors with moderate affinity (Ki values 1-4 microM), and to block adrenaline-elicited contractile responses in isolated guinea pig aortas. Our results indicate that ME10092 possesses a certain anti-oxidant profile. Thus, in a competitive manner and with low affinity it inhibited the bovine milk xanthine oxidase enzyme, as well as NAD(P)H oxidase driven oxyradical formation in membrane fractions isolated from the rat brain. By using electron paramagnetic resonance we here show that, after its systemic administration, ME10092 modulates the nitric oxide (NO) content in several tissues of the rat in a time-dependent manner. However, in vitro ME10092 inhibited the activities of nitric oxide synthases nNOS and eNOS, but not that of iNOS. Our data give evidence that the cardioprotective effect of ME10092 could be mediated thro...Continue Reading

References

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Jun 14, 2002·Cardiovascular Research·Qing-Dong WangLars Rydén
Jun 18, 2002·European Journal of Pharmacology·Maija DambrovaJarl E S Wikberg
Sep 5, 2002·Free Radical Biology & Medicine·Roger Harrison
Feb 25, 2003·British Journal of Pharmacology·Péter Ferdinandy, Richard Schulz

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Citations

Jul 28, 2005·Natural Product Reports·Roberto G S Berlinck, Miriam H Kossuga
Jan 16, 2010·International Immunopharmacology·Maija DambrovaEdgars Liepinsh

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