I. A. Kravchenko

Effect of Lauric Acid on Transdermal Penetration of Phenazepam In Vivo

We studied the effect of lauric acid on transdermal penetration of phenazepam in vivo. It was found that treatment with lauric acid 3-fold increased the maximum anticonvulsive effect of phenazepam applied in a transdermal therapeutic system in comparison with the control. Study of the pharmacokinetics of phenazepam transdermal therapeutic system showed its higher bioavailability in the presence of lauric acid (f = 0.9).

Synthesis, Physicochemical Properties, and Anticonvulsant Activity of the Gaba Complex with a Calix[4]Arene derivative

A complex based on 5,11,17,23-tetra-t-butyl-25,27-bis(carboxymethoxy)-26,28-dihydroxycalix[4]arene and ã-aminobutyric acid was synthesized. Complexation between the macromolecule and amino acid was confirmed using IR, UV, and PMR spectroscopy, mass spectrometry, and fluorimetry. UV spectrophotometric titration showed that the calix[4]arene derivative could form complexes of stoichiometry 1:1 and 2:1 (host:guest). The synthesized complex exhibited prolonged anticonvulsant activity, which was evaluated by determining the minimum effective doses of corazole inducing clonic-tonic convulsions and tonic extension.

Synthesis and anticonvulsant activity of 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones

A series of 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones were synthesized and their anticonvulsant properties were studied. It was found that 7-bromo-5-phenyl-3-cyclopropylmethyloxy derivative VIII had the highest anticonvulsant action among the synthesized compounds, the value of which was comparable with that of the reference compound 7-bromo-3-hydroxy-5-(2′-chloro)phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one (II). It was established that the 3-alkoxy-5-phenyl derivatives had higher anticonvulsant action than the 3-alkoxy-5-(2_-chloro)phenyl derivatives. The structures of compounds VIII and IX were determined by x-ray crystal and molecular structure analyses.

Effects of cholesterol and its esters on transdermal penetration of phenazepam

Cholesterol and its esters with aliphatic acids were studies as agents increasing the transdermal penetration of phenazepam when given transdermally in mice. Drug penetration was measured in terms of its pharmacological action (anticonvulsive effect on intravenous administration of 1% corasole). These studies showed that of the compounds studied, cholesteryl pelargonate had the greatest enhancing effect.

Effect of Skin Permeability Enhancers on the Transdermal Introduction of Phenazepam Studied in vitro

The growing interest in transdermal medicinal forms is related to their significant advantages such as the ability to prolong the action of the active drug component and stabilize its concentration on a constant level. This ensures a prolonged stationary pharmacological effect against the background of much less pronounced side effects [1]. In order to maintain the required concentration of a given drug in the organism, it is necessary to provide conditions for this drug to penetrate in sufficient amount through the horny layer of epidermis – the main barrier hindering penetration of foreign substances through the skin. Since most drugs are incapable of penetrating through the skin in sufficient amounts, there is a need to develop means for reversible control of the barrier properties of the horny layer. In connection with this, much attention is devoted to the search for effective skin permeability enhancers, capable of reversibly increasing the drug penetration, and to the study of the mechanisms of their action [2]. This work was aimed at determining the influence of some potential skin permeability enhancers upon transdermal introduction of phenazepam in vitro.

Biokinetics of transdermal therapeutic medicinal form of phenazepam.

We studied the rate of phenazepam absorption into the blood and its transport to the brain from a transdermal therapeutic system and bioavailability of the drug in this system. Hydrogel matrix consisting of polyvinyl alcohol and 1,2-propylene glycol was used for application. Transdermal application of 0.1–0.4 mg phenazepam in a dose of 14 mg/kg provided a stable level of this drug during application interval (1–48 h), while its bioavailability for blood plasma and brain was 0.63 and 0.2, respectively (determined for 0.4 mg phenazepam). The rate of drug penetration into the blood and brain was 46 and 60 ng/ml/h, respectively.

Synthesis and Anticonvulsant Activity of New Calix[4]Arene Derivatives Containing Gamma-Aminobutyric Acid Moieties

A series of novel mono- and disubstituted p-tert-butylcalix[4]arene derivatives functionalized with gamma-aminobutyric acid (GABA) and its methyl ester were synthesized and screened in vivo for anticonvulsant activity by determining the minimum effective doses of pentylenetetrazole inducing clonic-tonic convulsions and tonic extension. Calixarene derivative X with one acetic acid and one GABA ester on the lower rim of the macrocyclic scaffold was characterized as possessing prolonged anticonvulsant activity. A relationship between the pharmacological effect and the number of amino-acid residues was found. Disubstituted calixarenes IV and IX demonstrated higher anticonvulsant activity 24 h after administration than the monosubstituted analogs.

Synthesis and Anti-Inflammatory Activity of Novel Calix[4]Arene Derivatives Containing an Ibuprofen Residue

Novel derivatives based on calix[4]arene and ibuprofen were prepared. Physicochemical analysis methods were used to identify these compounds. Studies of their anti-inflammatory actions in a carrageenan edema model showed that these substances had greater anti-inflammatory effects than ibuprofen.

Synthesis and Anti-Inflammatory Activity of Ibuprofen Esters

The anti-inflammatory activities of new ibuprofen esters with alcohol residues of different lengths were studied. These compounds were found to have anti-inflammatory and antiedema activities comparable to and in some cases greater than those of equimolar quantities of ibuprofen.

Effects of Liquid Crystal Systems Based on Cholesterol Esters on Skin Permeability

The mechanisms of the influences of liquid crystal systems based on cholesterol esters on skin permeability were investigated. The effects of liquid crystal systems based on cholesterol esters on the transcutaneous penetration of phenazepam from transdermal therapeutic patches were studied in in vitro conditions. Changes in the fluidity of phospholipid liposomes and liposomes prepared from stratum corneum lipids were studied using fluorescence spectroscopy. Liquid crystal systems based on cholesterol were shown to be effective enhancers of skin permeability.