Conformation and kinetic characteristics of interactions between local anesthetics and aqueous solutions of hydroxypropylmethylcellulose.

Conformation and kinetic characteristics of the interactions of local anesthetics lidocaine (xycaine), tetracaine (dicaine), bupivacaine, and new RU-1117 compound with proven anesthetic activity with Visiton (1% hydroxypropylmethylcellulose in phosphate buffer) were studied. It was found that complex formation between the local anesthetics and hydroxypropylmethylcellulose is a time-dependent reversible process. The equilibrium is attained within 2.

Molecular mechanisms of vasoconstrictor action of imidazo[1,2-alpha]benzimidazole derivative RU-1117 possessing local anesthetic properties.

We studied the mechanisms of action of imidazobenzimidazole derivative RU-1117 on calcium homeostasis in myocytes isolated from rat thoracic aorta. In therapeutic concentrations, RU-1117 increased the content of free calcium ions due to their mobilization from intracellular depot via the IP3-dependent mechanisms. Antagonists of angiotensin II AT1-receptors irbesartan and, to greater extent, eprosartan abolished the calcium-mobilizing action of RU-1117.

Structural analysis of heart rhythm spectrogram in narcotized cats.

Eight types of peaks were revealed in the cardiac rhythm spectrum during acute experiments on vagotomized cats. Some peaks had no physiological nature and resulted from specificity of ECG processing by Fourier analysis, while others reflected myogenic reaction of the sinoatrial node (length-dependence of automaticity) to changes in venous return caused by respiratory-induced and other variations of the blood flow in the cardiovascular system.

Potentiation of GABA-activated currents by imidazobenzoimidazole derivative RU-353 in isolated cerebellum Purkinje cells.

Voltage clamp and concentration jump experiments performed on Purkinje cells isolated from rat cerebellum showed that novel imidazobenzoimidazole derivative RU-353 increased the amplitude of GABA-activated chlorine current in a dose-dependent manner (EC50=15 microM for the currents activated by 1 microM GABA). RU-353 shifted the GABA dose-response curve to the left, but produced no effect on the maximum response (EC50 in control and in the presence of 30 microM RU-353 were 6.9 and 2.

Kinetics of interaction of local anesthetics with human serum albumin.

We studied kinetic parameters of interaction of local anesthetics (lidocaine, tetracaine, bupivacaine, and two novel agents with proved local anesthetic potency RU-353 and RU-1117) with human serum albumin. Complexation of local anesthetics with human serum albumin is a time-dependent and reversible process; equilibrium was attained within 1.5-4.

Comparative assessment of conduction anesthesia produced by procaine, marcaine, richlocaine, and RU-353.

Conduction anesthesia of the vagus nerve produced by procaine (0.5%), marcaine (0.25%), richlocaine (0.

Antiedematous and edematous effects of local anesthetic RU-353 applied to various regions of the medulla oblongata.

Experiments on random-bred albino rats showed that application of local anesthetic RU-353 to the dorsal nuclei of the vagus nerve produced edematous or antiedematous effects in the lungs. Our findings open new vistas in prevention of centrogenous forms of water imbalance in the lungs.

A method for evaluation of conduction anesthesia.

We propose a new method for evaluation of conduction anesthesia in animals: by the degree of prolongation of cardiac cycle during vagus nerve stimulation by solitary electric discharges synchronous to the dominant ECG wave, proximally from the site of anesthetic application on the nerve.

Effect of imidazobenzoimidazole derivatives RU-353, RU-563, and lidocaine on cerebral circulation in rats.

We demonstrated a dose-dependent inhibitory effect of novel imidazobenzoimidazole derivatives RU-353 and RU-563 on cerebral blood flow and systemic blood pressure in narcotized rats. The effects of RU-353 increased, while the effect of RU-563 decreased with increasing the dose.

Pharmacokinetics and pharmacodynamics of a new local anesthetic agent.

We compared the effects of local anesthetics procaine, amethocaine (dicaine), bupivacaine, and a new agent RU-1148 on hydrolytic activity of human plasma butyrylcholinesterase. The butyrylcholinesterase-blocking activity of the test substances decreased in the following order: bupivacaine>amethocaine>procaine>RU-1148. The study of the capacity of these agents to form complexes with human plasma proteins and serum albumin showed that RU-1148 in therapeutic concentrations was transported by human serum albumin,beta-globulin, and acid glycoproteins.

Mechanisms underlying combined action of clonidine and local anesthetics.

We studied the mechanisms of combined action of clonidine and local anesthetics amethocaine and imidazo-benzimidazole derivative RU-1117. In contrast to amethocaine, RU-1117 in therapeutic concentrations binds to imidazoline receptors and, to a lesser extent, to alpha(2A)-adrenoceptors on human platelets. Clonidine and RU-1117 produce opposite effects on platelet aggregation induced by ADP in low concentrations.

Experimental approach to differentiation of the effects mediated by imidazole receptors and alpha2-adrenoceptors on platelets.

We studied parameters of specific binding for various ligands of imidazole receptors and alpha2-adrenoceptors on human platelets. Pharmacological activity of compounds was evaluated by their effects on platelet aggregation induced by ADP in low concentrations (0.125-1.