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Abstract. Drug-platelet agregation receptor interaction of pro and antiaggregants is only possible for a certain distribution of electron density in the molecule that generates electron-rich regions. Molecular electrostatic potential can be used to assess the cuantomolecular lipophilicity, because it characterizes the polarity of a certain region on the van der Waals surface of the molecule. Energy difference between the levels HOMO and LUMO is explaining the stability of the molecule, a low value indicating that the molecule is highly reactive, the most stable molecule is adrenaline. The tendency of donation - acceptance of electrons is described by electronegativity. Greater electronegativity is presented by thiol active metabolite of clopidogrel explaining bigger reactivity of this substance. In case of antagonism between proaggregant adrenaline and antiaggregant clopidogrel it was found that there is not an interaction between the two molecules but only competition for receptor.
Keywords: clopidogrel, adrenaline, electron density, proaggregant, antiaggregant
1. INTRODUCTION
In a fundamental physicochemical approach to platelet aggregation phenomena based on the Dereaghin-Landau Verwey Overbeek theory, the stability of blood and the lack of platelet aggregation is the consequence of their negative electrical charge and the rejection between the double electrical layers formed at the membranes. Classical DLVO forces alone are not sufficient to accurately predict aggregation behavior. More recently, theory was extended to include ionic, steric, elastic [1] and osmotic forces [2-3] in so called extended DLVO theory (XDLVO). In this physico-chemical context all negative charged molecules which adsorb at membranes have to present antiagregant activity and all positively charged are potentially proaggregant. This is more or less true in vitro but, in vivo , there are only a few antiaggregant drugs, essential treatment of cardiovascular and neurological stroke being based on aspirine and clopidogrel.
Intrinsic platelet aggregation is very low and is not directly measurable. It is much elevated before and immediately after vascular accidents, involving an increased risk of relapse or transient vascular accident. As a result, antiaggregation treatment is mandatory in all cases, but the treatment with a drug or combination of antiaggregation drugs is one of long duration. Instead of the effect on intrinsic aggregation, it is evaluated the effect of antiaggregant treatments on aggregation induced by a proaggregate, usually adrenaline. The challenge of antiaggregant therapy is the...