31P NMR and FTIR studies on the interaction of phosphorylacetohydrazides with dipalmitoyl phosphatidylcholine model membranes

Abstract

The effect of original synthetic nootropic drugs (phosphorylacetohydrazides) on the physical properties of the dipalmitoyl phosphatidylcholine (DPPC) membranes was studied by 3lp nuclear magnetic resonance and Fourier transform infrared spectroscopies. Ir has been shown that the tested preparations reduce the phase transition temperature, widen the transition interval, suppress pretransition, render some condensing effect on the gel phase and essentially disorder the lipid bilayer in the liquid-crystalline state. The obtained results are in agreement with the suggested rnechanism of the primary pharmacological effect of nootropic preparations. According to this mechanism, the drug molecules penetrate into the hydrophilic region of the bilayer, interacting closely with the polar groups of DPPC, disturbing the bilayer organization and leading to polymorphism. By taking into account that the main property of nootropic preparations is to improve processes of training and memory, we suppose that the new lipid-drug organization of phospholipidic membranes and lipid polymorphism are the necessary steps of the nootropic activity. The similarity of molecular mechanisms of various nootropic drug effects on the lipid bilayer allows us to suppose that the positive effect of nootropics on the synaptic transmission may be governed by their influence on the phase transition of the lipid component of the synaptic membranes at the stage of the neurotransmitter release.