Comparative analysis of neuroprotective activity of new chemical agent Vp and piracetam.

The effect of new agent Vp (9-butylamine-3,3-dimethyl-3,4-dihydroacridine-1(2H) hydrochloride) on lifetime of isolated mechanoreceptive crayfish neurons was evaluated by the duration of its impulse activity. Vp significantly and dose-dependently prolonged the lifetime of both spontaneously degrading neurons and neurons degrading under conditions of inhibition of various stages of the energy metabolism: glycolysis and oxidative phosphorylation. The effect of Vp in a concentration of 10(-7) M surpassed that of amiridine. Piracetam also prolonged the lifetime of spontaneously degrading neurons, but only in very high concentration (10(-2) M). It is concluded that Vp possesses a neuroprotective activity.

Amiridin and tacrine modulation of the activity and plasticity of the cholinoreceptors of neurons of the common snail: phenomenology and mechanisms.

The influence of amiridin and tacrine on the membrane potential, activity, and plasticity of cholinoreceptors was investigated using the methods of recording of intracellular potentials and transmembrane currents in identified RPa3 and LPa3 neurons of the common snail. Amiridin and tacrine (1-100 mumole/liter) do not exert appreciable influences on the membrane potential of the cells. Both compounds modulate the activity of cholinoreceptors, judging from their influence on the inward current induced by local application of the acetylcholine: the duration of the ACh current increases and its amplitude varies biphasically (a short-latency increase is succeeded by a decrease). Amiridin and tacrine intensify the extinction of the ACh current induced by repeated applications of ACh to the soma. The acetylcholinesterase inhibitor, physostigmine, exerts a similar modulatory influence on the ACh current and on its extinction, and also prevents the manifestation of the effects of amiridin and tacrine. Amiridin and physostigmine directly influence the cholinoreceptors and the ionic membrane channels controlled by them by similarly altering the voltage-current characteristics (VAC) of the ACh current, and by shifting the reversal potential of the ACh current in the negative direction, bringing it closer to the equilibrium potential for chloride ions; this may be interpreted as a result of the nonidentical action of these compounds on the various ionic currents controlled by cholinoreceptors. The hypothesis is advanced that the modulatory influence of amiridin, tacrine, and physostigmine on the activity and plasticity of the cholinoreceptors is governed by their direct membrane-cytoplasmic action.

[The amiridin and tacrine modulation of the cholinoreceptor activity and plasticity of snail neurons: the phenomenology and mechanisms]. / Moduliatsiia ampiridinom i takrinom aktivnosti i plastichnosti kholinoretseptorov neironov vinogradnoi ulitki: fenomenologiia i mekhanizmy.

The effects of amiridine and tacrine on the membrane potential, activity and plasticity of cholinoreceptors have been studied using the recording of intracellular and transmembrane currents in identified neurons of Helix lucorum. Amiridine and tacrine (1-100 mcM) have no noticeable effects on the membrane potential of the cells. Both compounds modulate the activity of cholinoreceptors to judge from their influence on the inward current induced by the local acetylcholine (ACh) application: they increase the duration of the current with a two-phase effect on the amplitude (a short-latent intensification with a following decrease). Amiridine and tacrine intensify ACh current extinction induced by repeated ACh application to the soma. Acetylcholinesterase inhibitor physostigmine has a similar modulating effect on ACh current and its extinction. It impedes the modulating effects of amiridine and tacrine. Amiridine and physostigmine directly affect cholinoreceptors and ion channels controlled by them changing in a similar way the current-voltage curves of ACh-current and approximating it to the equilibrium potential of chloride ions. Modulating effects of amiridine, tacrine and physostigmine on the activity and plasticity of cholinoreceptors may be supposed to be caused by their direct membrane-cytoplasmic action.

[A comparative study on the effects of amiridin on learning and memory of old rats during passive avoidance test]. / Sravnitel'noe izuchenie vliianiia amiridina na obuchenie i pamiat' starykh krys v teste uslovnoi reaktsii passivnogo izbeganiia.

18-month rats showed much less learning ability in comparison with that of 3-month rats. 20-days treatment of old rats with amiridin, tacrine, and piracetam improved latency in passive avoidance test to the level of 3-month rats. The activity of acetylcholine esterase (AChE) from homogenates of old rat cortex was reduced as compared with that of young rats. After treatment with amiridin the activity of the enzyme remained unchanged, tacrine stimulate the decrease of activity of AChE while piracetam increased activity of AChE to the level of 3-month rats. The aging of rats is followed by the reduction of unsaturated fatty acids, the increase of cholesterol content and the increase of microviscosity of membranes of brain synaptosomes. Multiple treatment with amiridin, piracetam and tacrine normalized these indices.

[Experimental study of the effects of amiridin and tacrine on learning and memory]. / Eksperimental'noe izuchenie vliianiia amiridina i takrina na obuchenie i pamiat'.

The authors studied the influence of amiridin and tacrine on learning and memory in mice and rat by passive avoidance conditioning test at norm and under scopolamine induced amnesia as well as of their effect on acetylcholine esterase (AChE) activity in brain cortex homogenates. Amiridin in doses 0.1 and 0.2 mg/kg showed a beneficial action on conditioning in untreated animals, its effect being comparable with that of piracetam. Tacrine was ineffective. In scopolamine treated animals amiridin and tacrine showed anti-amnestic action at dose of 0.1 mg/kg which was found ineffective with respect to AChE activity. The data suggests that the ameliorating effect of amiridin and tacrine on cognitive abilities in patients with senile dementia is not related their anticholinesterase properties.

[Study of anti-amnesic activity of amiridin in a model of amnesic syndrome]. / Izuchenie antiamnesticheskoi aktivnosti amiridina na modeli amnesticheskogo sindroma.

The model of amnestic syndrome obtained by treatment with scopolamine during 20 days in rats was used to study anti-amnesic activity of amiridin in comparison with that of tacrine, physostigmine and piracetam. Multiple injection of Sc resulted in significant deterioration of rats, performance in passive avoidance test. Behavioral disorders were accompanied by such changes in lipid composition of brain synaptosomes which indicated a decreased membrane fluidity. Amiridin and tacrine as well as piracetam showed anti-amnesic action which in the course of treatment correlated with their normalizing effect on lipid content of synaptosomes. The diverse effect of amiridin and tacrine with respect to physostigmine implies that the former drugs can't be attributed to anticholinesterase preparations which are traditionally used in the treatment of Alzheimer disease.

[Antibody formation to o-aminoazotoluene via the administration of conjugated antigens synthesized by enzymatic and chemical methods]. / Obrazovanie antitel k o-aminoazotoluolu pri vvedenii kon''iugirovannykh antigenov, sintezirovannykh fermentativnymi i khimicheskimi metodami.

Two new methods are developed for synthesis of conjugated antigens of o-aminoazotoluene-bovine serum albumin (o-AAT--BSA): (1) from the microsomal fraction of the guinea pig liver which contains the cytochrome-P-450-dependent monooxygenase enzymic system and (2) from the m-chloroperbenzoic acid. A possible mechanism of the covalent binding of o-AAT with albumin under the effect of monooxigenases and of their chemical model is considered. Differences of antigenic determinants in conjugated antigens of o-AAT--BSA synthetized by the chemical and enzymic methods are detected.

[Preparation of antibodies against o-aminoazotoluene using chemically and enzymatically synthesized conjugated antigens]. / Poluchenie antitel k o-aminoazotoluolu s pomoshch'iu sintezirovannykh khimicheskim i fermentativnym metodami kon''iugirovannykh antigenov.

Two methods are developed for synthesis of conjugated antigens to o-aminoazotoluene (o-AAT)-albumin: the enzymatic method--using horseradish peroxidase (HP) and the chemical one--diazomethod. A possible mechanism is suggested for the covalent binding of o-AAT to albumin which is catalyzed by HP. Antibodies to o-AAT are obtained by immunization of animals. An essential difference is established for antigenic o-AAT determinants in conjugates synthesized by the enzymatic and chemical methods.

[Phospholipase C of fungi and staphylococci]. / Fosfolipaza C u gribov i stafilokokkov

The activity of phospholipase was studied in the cultural broth and cell extract of 112 strains of fungi and yeasts. The endoenzyme was detected in 19 strains of mycelial fungi, the exoenzyme was found in Mucor hiemalis 50 and Aspergillus niger 117. Phospholipase C of M. hiemalis was purified and compared to phospholipase of staphylococci. The values of Km are 8.9 and 1.07 mM, respectively, for the fungal and staphylococcal enzymes.