Suprastin (Chloropyramine) Causes Proarrhythmic Deterioration of Excitation Conduction, Depolarization and Potentiates Adrenergic Automaticity in the Pulmonary Veins Myocardium.

A number of pharmacological drugs have side effects that contribute to the occurrence of atrial fibrillation, the most common type of cardiac rhythm disorders. The clinical use of antihistamines is widespread; however, information regarding their anti- and/or proarrhythmic effects is contradictory. In this work, we studied the effects and mechanisms of the potential proarrhythmic action of the first-generation antihistamine chloropyramine (Suprastin) in the atrial myocardium and pulmonary vein (PV) myocardial tissue. In PV, chloropyramine caused depolarization of the resting potential and led to reduction of excitation wave conduction. These effects are likely due to suppression of the inward rectifier potassium current (IK1). In presence of epinephrine, chloropyramine induced spontaneous automaticity in the PV and could not be suppressed by atrial pacing. Chloropyramine change functional characteristics of PV and contribute to occurrence of atrial fibrillation. It should be noted that chloropyramine does not provoke atrial tachyarrhythmias, but create conditions for their occurrence during physical exercise and sympathetic stimulation.

Effects of Non-Opiate Analogue of Leu-Enkephalin on the Ion Currents, Number of Nucleoli, and p53 Expression in Isolated Cardiomyocytes of Albino Rats.

Acute exposure of isolated ventricular cardiomyocytes to non-opiate analogue of leu-enkephalin (NALE peptide: Phe-D-Ala-Gly-Phe-Leu-Arg) in a concentration of 100 µg/liter and 6-h incubation in NALE solution did not significantly change ATP-dependent K+ current, L-type Ca2+ current, p53 protein expression, and number of nucleoli in the cardiomyocyte nuclei. Incubation of cardiomyocytes with NALE (100 µg/liter) in combination with NOP receptor blocker J-113397 (1 mg/liter) was followed by an increase in Ca2+ L-type current and the number of p53+ cells. The exposure of cardiomyocytes to NALE in a concentration 1000 µg/liter induced similar changes in the studied parameters (increase in Ca2+ L-type current and number of p53+ cardiomyocytes); an increase in the mean number of nucleoli was also observed. Our findings suggest that NALE peptide has direct effect on cardiomyocytes and NOP receptors are involved in this effect.

The Dependence of the Electrophysiological Effects of Class III Antiarrhythmic Drug Refralon on the Frequency of Myocardium Activation.

We studied the frequency dependence of the effects of the novel Russian class III antiarrhythmic drug refralon on the duration of action potentials (AP) in rabbit ventricular myocardium. The absence of an inverse frequency dependence of AP prolongation was demonstrated: the effects of refralon at stimulation frequency of 1 Hz were stronger than at 0.1 Hz. The patch-clamp experiments with recording of rapid delayed rectifier potassium current IKr in a heterologous expression system showed that the blocking effect of refralon developed significantly faster at 2 Hz depolarization frequency than at 0.2 Hz. This feature of refralon distinguishes it among the majority of other class III drugs (sotalol, dofetilide, E-4031) and explains the relatively high safety of this drug together with its high efficacy.

Gadolinium as an Inhibitor of Ionic Currents in Isolated Rat Ventricular Cardiomyocytes.

The whole-cell patch-clamp technique was used to examine the effect of gadolinium Gd3+ (a non-specific blocker of mechanically gated current IMGCh, a component of late current IL) on ionic currents in insolated rat ventricular cardiomyocytes alone and in combination with the blockers of L-type calcium currents (ICaL) nifedipine (10 µM) or verapamil (1 µM). In K+in/K+out or Cs+in/Cs+out media, blockade of ICaL produced no effect on IL at negative potentials, but inhibited IL at positive ones. In K+in/K+out medium, Gd3+ (5 µM) decreased the net persistent current (Inp) at -45 mV from 198.6±6.4 to 96.7±9.5 pA over 15 min. Gd3+ alone or in combination with ICaL blockers shifted the reversal potential of IL to more negative values. At negative potentials, Gd3+ decreased IK1 and inward current including IMGCh. At positive potentials, Gd3+ alone or in combination with ICaL blockers decreased IL. When applied for 15 min in Cs+in/Cs+out medium at -45 mV, Gd3+ produced no effect on net current and inward and outward components of IL. Thus, Gd3+ can be viewed as a specific blocker of IMGCh only in Cs+ medium.

[Catecholamine excretion in patients with eating disorders].

OBJECTIVE: To compare clinical features of eating disorders and parameters of monoamine metabolism. MATERIAL AND METHODS: Authors examined 21 patients with eating disorders during 2008-2011 using clinical/psychopathological method. To evaluate the status of monoamine neuromediator system, urine levels of dopamine, noradrenalin and adrenaline excretion were measured using high-yield liquid chromatography with electrochemical detection. The reference group included 26 sex- and age-matched volunteers. RESULTS AND CONCLUSION: The common patterns of the pathogenesis of compulsive urges of different origin were identified. The results indicate not only nonspecific changes in catecholamine systems of patients with eating disorders associated with different stress disorders but also demonstrate the pathogenetic correlations between dopaminergic activity and clinical symptoms of addiction.

Changes in electrical activity of working myocardium under condition of if current inhibition.

The study examined the effect of ZD7288, a blocker of hyperpolarization-activated "funny" current If, on electrical activity in working atrial and ventricular myocardium in rats. In concentrations range from 3×10(-6) to 3×10(-5) M, the agent significantly increased the duration of action potentials at 50 and 90% repolarization levels in both atrial and ventricular myocardium at the fixed stimulation rate of 5 Hz. The blocker affected neither resting potential nor the upstroke velocity of action potential. In patch-clamp experiments, ZD7288 selectively inhibited If current, but produced no effect on delayed rectifier potassium currents that determine the rate of repolarization. The described effects of ZD7288 are not related to its non-specific effects on the ionic currents except If.

Processes of DNA methylation are involved in the mechanisms of amnesia induction and conditioned food aversion memory reconsolidation.

We studied the role of DNA methylation in the mechanisms of amnesia in edible snails, which was induced by impairment of conditioned food aversion memory reconsolidation with NMDA glutamate receptor antagonist. The effects of DNA methyltransferase inhibitors were shown to depend on the stage of amnesia. At the early stage of amnesia (day 3 after induction), injections of methyltransferase inhibitors in combination with conditioned food stimulus (reminder) were followed by memory recovery. Application of inhibitors in the absence of the reminder was ineffective. Methyltransferase inhibitors were ineffective at the late stage of amnesia (day 10). Our results suggest that the presentation of reminding conditioned stimuli is followed by reactivation of amnesia. Methylation or demethylation of DNA in nerve cells serves as one of the key mechanisms for amnesia.

Catecholamines and their metabolites in the brain and urine of rats with experimental Parkinson's disease.

The content of catecholamines and their metabolites in the brain and the relationship between cerebral catecholamine levels and their urinary excretion were studied in rats with 6-OHDA-induced hemiparkinsonism. 6-OHDA reduced brain concentrations of dopamine, DOPAC, and homovanilic acid and urinary excretion of dopamine, dioxyphenilalanine, and DOPAC by more than 90%. A positive correlation was found between the concentrations of these metabolites in the urine and striatum. Measurement of urinary catecholamines and their metabolites is a perspective test for evaluating the status of the dopaminergic nigrosostriate system of the brain in experimental parkinsonism.

Complex analysis of efficiency of transplantation of embryonic nerve tissue to rats with hemiparkinsonism.

Effect of transplantation of embryonic ventral mesencephalon preparation containing dopaminergic neurons on repair of the dopaminergic nigrostriatal system was studied in rats with hemiparkinsonism induced by 6-hydroxydopamine. Transplantation of embryonic ventral mesencephalon into denervated striatum led to a more than 50% decrease in apomorphine-induced rotation, recovery of dopamine and DOPAC levels in the brain, and to an increase in DOPAC excretion and the DOPAC-dopamine ratio in daily urine of rats with hemiparkinsonism. Dopaminergic neurons of the transplant survived, forming a network of tyrosine hydroxylase-positive processes growing beyond the transplant and reinnervating the adjacent compartments of the striatum. A positive correlation between urinary excretion of DOPAC and brain concentration of dopamine was revealed in denervated rats after transplantation of ventral mesencephalon. Intrastriatal transplantation of cell preparations of embryonic striatum containing no dopaminergic neurons and isolated local injury to the striatum did not affect regeneration of the denervated nigrostratal system.

[Relationship of free and conjugated forms of catecholamines in depressive disorders in psychopathic personalities]. / Sootnoshenie svobodnykh i kon''iugirovannykh form katekholaminov pri depressivnykh rasstroistvakh u psikhopaticheskikh lichnostei.

The study was undertaken to examine the content of free and conjugated forms of norepinephrine, dopamine, epinephrine in the daily urine and blood plasma of psychopathic patients during varying severity depressive disorders. To isolate the conjugated forms, hot acid hydrolysis was applied, catecholamines were measured by the procedures based on high performance liquid chromatography with electrochemical detection. Patients with the most marked clinical signs of depressions were found to have the most profound urinary and blood shortage of free forms of dopamine and norepinephrine, as compared with the controls, which was associated with the most intensive conjugation of these catecholamines. Thus, it may be supposed that disturbances of the catecholamine conjugation systems are one of the neurochemical mechanisms underlying the development of affective disorders.

[Determination of free and conjugated catecholamines, 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid in the urine and blood plasma by high pressure liquid chromatography]. / Opredelenie svobodnykh i kon'iugirovannykh form katekholaminov, 3,4-dioksifenilalanina, 3,4-dioksifeniluksusnoi kisloty v moche i plazme krovi s ispol'zovaniem vysokoéffektivnoi zhidkostnoi khromatografii.

A method for simultaneous measurement of free and conjugated forms of adrenalin, noradrenaline, dopamine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylacetic acid in the blood plasma and urine by high-pressure liquid chromatography with electrochemical detector has been developed. The levels of the said substances in 36 normal volunteers and 20 patients with mental disorders are presented. Simultaneous measurements of excretion of free catecholamines and their conjugates permitted a more complete characterization of catecholamine metabolism, which is important for understanding the mechanisms of disorders in catecholamine system in various diseases.

[Monoamine metabolism in different forms of paraphilias]. / Obmen monoaminov pri razlichnykh formakh parafilii.

42 persons which commited crime sexual actions were examined in terms of clinical and neurochemical investigations. The sexual behaviours of 31 patients from this group were associated with sexual inclination pathology--with paraphilia. The patients were divided into 2 groups namely with compulsive form of paraphilia (13 individuals) and without compulsive disturbances (18 patients). Both free and conjugated forms of norepinephrine (NA), dopamine (DA), dihyroxyphenylalanine (DOPA) and dihyroxyphenylacetic acid (DOPAC) were measured in serum and daily urine as well as serotonin concentration was estimated in blood plasma and platelets. The rate of 3H-serotonin uptake into platelets (Vmax) was also investigated. It was determined that Vmax, free and especially conjugated forms of NA, DA, DOPAC levels were significantly higher in patients with compulsive forms of paraphilia. It was supposed that monoamine mechanisms may be operated in psychopathological variations of the crime sexual behaviour.

[Catecholamines and the dopamine-beta-hydroxylase activity of the blood plasma in motor pathology in children: the role of central and peripheral mechanisms]. / Katekholaminy i aktivnost' dofamin-beta-gidroksilazy plazmy krovi pri dvigatel'noi patologii u detei: rol' tsentral'nykh i perifericheskikh mekhanizmov.

Plasma catecholamine levels and serum dopamine-beta-hydrolase (D beta H) activity were investigated using high-performance chromatography and spectrophotometry, respectively, in 32 patients aged 10-14 with various motor pathology. Group 1 patients (21 children with spastic diplegia and clinical signs of central catecholaminergic neuromediation deficiency) received Nakom in a single daily dose 60 mg in the morning. The treatment produced a good clinical effect. Six children of group 2 with hereditary degenerative cerebral, spinal, nervous diseases and 5 children of group 3 with lower spastic paraplegia consequent to spinal cord trauma inflicted 6-12 months: before received Nakom in a single daily dose 30 mg in the morning for 14 days. The treatment in them resulted in an essential decrease of pelvic dysfunctions. All the children had a high DOPA level in blood plasma irrespective of the group and Nakom administration. Pretreatment dopamine (DA) levels were different: the least in cerebral palsy patients (0.019 +/- 0.01 ng/ml), the highest in group 2 (p < 0.05), in children with spinal cord pathology it was higher than normal and higher than in group 1 (p < 0.001). Nakom treatment promoted DA normalization in all the groups. Norepinephrine (NE) concentrations were very low in all the patients correlating with the degenerative process degree and did not change in response to Nakom administration. D beta H activity was inhibited in all the groups, especially in the spinal patients. Nakom increased both D beta H activity (p < 0.01) and motor activity. Thus, an increased DOPA level is plasma is not specific for nervous diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

[The neurochemical mechanisms underlying possible recurrences of alcoholism]. / Izuchenie nekotorykh nerokhimicheskikh mekhanizmov, lezhashchikh v osnove vozmozhnykh retsidivov alkogolizma.

Experiments on chronic alcoholized rats revealed the similar changes in brain dopamine receptors, in brain and blood catecholamines as well as in blood cyclic adenosine monophosphate during both short- and long-term alcohol deprivation. It is concluded that such changes may form material basis for alcoholism relapses.