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Superfusion of the isolated frog spinal cord by the Ringer solution containing arecoline (10 mumol/l) evoked depolarization and increase of the input resistance and PSP amplitude of motoneurons. Depolarizing electrotonic potentials and reflex discharges in the ventral roots also increased, but duration of dorsal root potentials decreased. The observed arecoline facilitation of synaptic transmission in the spinal cord has postsynaptic nature evoked by motoneuron M2-cholinoreceptor activation and bound to an increase of the cyclic nucleotide metabolism. Arecoline inhibited the synaptic transmission in the spinal cord under conditions when its postsynaptic action was eliminated. This effect was due to presynaptic M1-cholinoreceptor activation without changing the cyclic nucleotide metabolism.

It has been shown in experiments on rat vas deferens that melipramine, harmane and 3-methylharman in low concentrations of the order of 10(-8)--10(-6) M increase the contraction of the vas deference induced by noradrenaline and transmural stimulation. Meanwhile in higher concentrations (10(-6)--4 X 10(-5) M) they have been discovered to decrease this effect (except for harmane). In low concentrations harmane and 3-methylharman competitively remove the inhibitory effect of clonidine on the transmural stimulation-induced contractions. It is inferred that harmane and methylharman are competitive blockers of presynaptic alpha 2-adrenoceptors in adrenergic synapses.

Experiments on the neurons of isolated spinal cord of rats aged 9-14 days have revealed that like picrotoxin, the neuroleptics reduce the GABA-induced depolarization of primary afferents, hyperpolarization of the motoneurons and inhibition of the function of the interneurons which exercise the inhibitory control of motoneuronal activity. The highest GABA-lytic activity was displayed by the butirophenon derivatives (droperidol and haloperidol). Triphthazin slightly yields to these drugs as regards the activity. Aminazin and levomepromazin have a moderate GABA-lytic activity, whereas thioridazin and ftorphenazin have none. A possible role of the GABA-lytic activity of the neuroleptics in their antipsychotic action is discussed.

Tryptamine has been studied for its effect on the 5-hydroxytryptamine-induced responses of the dorsal root ganglion neurons in rat with intracellular registration of the membrane potential and conductance and application of drugs from micropipettes under pressure. It was found that tryptamine applied in high concentrations acted like 5-hydroxytryptamine; but in the concentration range when it has no effect on the membrane potential and membrane conductance it either enhanced (10(-7) mol/l) or diminished (10(-5) mol/l) 5-hydroxytryptamine responses mediated by 5-HT1A- but not by 5-HT2-receptors. Harmane acted like tryptamine, but its derivatives either only enhanced or only inhibited the 5-hydroxytryptamine effects. The allosterical nature of 5-hydroxytryptamine-modulating action of tryptamine, harmane and its derivatives is discussed.

Local micro-injection of dophamine, norepinephrine and serotonin into the dorsal hippocampus of rats in doses of 5gamma does not affect the muscle tone and spontaneous motor activity of the animals, but lengthens the latent period of the conditioned avoidance reflex (CAR). When administered into the hippocampus in the same dose 15 minutes after injection of lithium chloride (1gamma equiv) dophamine inhibits stronger the CAR and noticeably stimulates the motor activity. At the same time, a preliminary injection of lithium cloride into the hippocampus does not change the action of norepinephrine and serotonin on the length of the latent CAR period, but, when used against the background of lithium chloride, norepinephrine depresses the motor activity.

The activity of neuroleptics and phentolamine as substances which counteract the direct hyperpolarizing effect of noradrenaline and dopamine on motoneurons of the rat isolated spinal cord has been determined quantitatively. The adrenolytic effect of the neuroleptics studied varied 1000fold while the antidopamine activity 250fold. The postsynaptic activity of neuroleptics is compared with the ability to increase the radioactive noradrenaline release by electrostimulated slices of the rat brain cortex. It has been discovered that haloperidol dominates in the presynaptic while chlorpromazine and droperidol in the postsynaptic anticatecholaminergic action. Flufenazine exhibits an equal pre- and postsynaptic action.

Serotonin caused contracion of the smooth muscles of the deferent duct and of the strip of rat stomach, acting upon the D-serotonin receptors. Only a small portion of its contractile effect (about 10--14%) was caused by the release of endogenous catecholamines. The action of serotonin on the strip of the rat stomach was accompanied by an increase of its entrance into the cells of Ca45 and Na22 isotopes. The concentration turn of the concentration-effect curve of serotonin on the stomach strip was connected with the accumulation of sodium ions in the cells.

Application of 5-hydroxytryptamine (5-HT) (3 x 10(-5) M) on the rat lumbar dorsal ganglia (RDG) induced membrane depolarization with increased input resistance in 30% of neurons, hyperpolarization with decreased input resistance in 30% of neurons and mixed responses in 40% of neurons. Methysergide and amitriptyline (10(-6) M) blocked depolarizing but not hyperpolarizing effects of 5-HT. Propranolol (3 x 10(-6) M) was inactive in respect to both 5-HT responses. 5-HT depolarizing responses of RDG neurons were mediated by 5-HT2 receptors activation and decreased membrane potassium conductivity; 5-HT hyperpolarizing responses were mediated by 5-HT1A receptor activation and increased potassium conductivity. RDG neurons seem to be an interesting model for the investigation of central 5-HT receptor mechanism.

In experiments on albino rats on the model of "cotton wool granuloma" it was found that non-steroidal anti-inflammatory agents inhibited the growth of the granulation and fibrous tissue that was followed by a normal decrease of contents of protein and RNA but not DNA in it. By their effect on RNA and granuloma weight butadione and mefenamic acid are significantly more active than antipyrine.

It has been shown in experiments on rat cortex slices preincubated with 3H-GABA that chlorodiazepoxide (10(-6), 3.10(-5) M) does not change basal and electric stimulation-induced release of the label. It has been also shown that it does not eliminate the autoinhibitory effect of GABA on electric stimulation-induced release of 3H-GABA. However, harmane and some other (but not all) derivatives given at the same concentrations increase 3H-GABA release induced by electric stimulation and abolish the inhibitory effect of GABA without changing or slightly raising spontaneous release of 3H-GABA. It is concluded that harmane enhances the electrically stimulated release of the transmitter by GABAergic axons whatever the effect on benzodiazepine-binding areas of GABA receptors.

When employed in high concentrations (1-10(-5)-1-10(-3) g/ml) acetylcholine (ACC) causes an accrued uptake of Na22 and liberation of Rb86 (K) from smooth muscles of the rat's stomach. An increased release of Ca45 occurs in concentrations of 1-10(-7) g/ml and higher. The contractile reaction is recorded under the action of lower ACC concentrations (starting from 1-10(-9) g/ml). The observed changes in the ionic permeability and tonicity are due to the ACC action on the M-cholinoreceptors of the muscles. A comparison of emipirical relation between the effects and the concentration against the theoretical one showed that it is only the incorporation of Na22, liberation of Rb86 pand the contractile reaction in a depolarizing solution that adequately reflect the ACC interaction with cholinoreceptors of the smooth muscles in the rat's stomach.

In experiments on superfused cerebral hemispheric cortex slices of rats preincubated with 3H-gamma aminobutyric acid (3H-GABA), 3H-serotonin (3H-ST) or 3H-noradrenaline (3H-NA) it was shown that benzodiazepine tranquillizers (chlordiazepoxide and diazepam at the concentration of 3 X 10(-5) M) fail to change basal and slice electrostimulation-induced release of 3H-GABA, depress presynaptic release of 3H-NA and significantly enhance impulse release of 3H-ST. In contrast to benzodiazepine tranquillizers, harmane and its derivatives administered at the same concentration enhance slice electrostimulation-induced release of 3H-GABA, 3H-ST and 3H-NA.

Experiments on an isolated spinal cord of 8-15-day-old rats have shown that one of the possible mechanisms of the GABA-potentiating action of the benzodiazepine tranquilizer, chlorodiazepoxide, may be a decrease in the intraneuronal concentration of Ca2+. This is evidenced by the enhancement of the GABA-potentiating action of chlorodiazepoxide under Ca2+ deficiency in the medium and in the presence of the blockers of the voltage-dependent Ca2+ ionic channels--Mn2+ and Co2+, and by the reduction of the effect in question under Ca2+ excess in the medium and in the presence of the K+ channels blockers--tetraethylammonium and 4-aminopyridine. The GABA-potentiating action of harmane is likely to be related to the blockade of the voltage-dependent K+ channels and elevation of the intracellular concentration of Ca2+.

Activating (0.3-3 microM) or inhibitory (0.03-0.3 mM) effects of dopamine (DA) in the absence of Ca2+, and its inhibitory effect in the presence of Ca2+ on Na,K-ATPase activity of synaptosomes from the caudate nucleus of the rat brain were confirmed. Na,K-ATPase was shown to be inhibited by 6 neuroleptics, with the degree of inhibition stronger in the presence of Ca2+. It was found that: 1) the biphasic or monophasic nature of DA action on Na,K-ATPase activity was preserved in the presence of neuroleptics, 2) DA enhances the inhibitory effects of neuroleptics on the enzyme, 3) the inhibitory effects of DA on Na,K-ATPase are enhanced by Ca2+ ions. The mechanisms of the modifying action of DA on synaptosomal Na,K-ATPase are discussed.

Experiments on an isolated spinal cord of rats aged 9-15 days have shown that harmane (10(-7)-10(-5) M) enhances GABA-induced (1.10(-4) M) depolarization of primary afferents and hyperpolarization of motoneurones. The GABA-potentiating action of harmane on primary afferents is depicted by a bell-shaped curve with a maximum at 10(-5) M. The action is more pronounced the higher the concentration of chlorine ions in the medium. Harmane (10(-6)-10(-4) M) enhances spontaneous neuronal activity and evoked synaptic potentials (mono- and polysynaptic potentials of the ventral and dorsal roots) at the concentrations at which it exerts a direct depolarizing action on motoneurones and primary afferents. At higher concentrations the stimulant activity of harmane (10(-5)-10(-4) M) counteracts its GABA-potentiating effects.

The membrane potential and conductance alterations of rat dorsal root ganglion neurons evoked by serotonin applied in bath or from a micropipette under pressure have been studied by intracellular technique. Serotonin application evoked depolarization with a decrease in membrane conductance and hyperpolarization with an increase in its conductance. A part of depolarization responses mediated by 5-HT2 receptor activation were independent of intracellular AMP concentration and associated with blockade of M-current channels. The other part of depolarizing and all hyperpolarizing responses mediated by 5-HT1A receptor activation were depressed by pertussis toxin and considerably modulated by intracellular AMP alterations. These responses were shown to be associated with disturbances in the function of AMP-dependent potassium ionic channels.

Superfusion of isolated hemisected spinal cord of 9-13 day old rats by solution containing noradrenaline induced de- or hyperpolarization of motoneurons depending on amine concentrations. Both effects resulted from a direct influence of amine upon motoneurons since they remained in the medium with abundance of Mg++ions and deficit of Ca++ions. Depolarization and hyperpolarization of motoneurons induced by noradrenaline was depressed by alpha-adrenoblockators. Depolarization of motoneurons induced by dopamine was suppressed in medium with abundance of Mg++ions. Hyperpolarization of motoneurons induced by dopamine was suppressed by haloperidol but remained unchanged under phentolamine. Depolarization of motoneurons induced by serotonin and its metabolities-mexamine, kynurenine and 3-oxyanthranilic acid-remained in the medium with abundance of Mg++ions and deficit of Ca++ions and was depressed by deseril and BAS. Hyperpolarization effect of serotonin appearing in some experiments under high concentration of serotonin (10(-4)-10(-3) M) was suppressed in medium with abundance of Mg++ions and in the presence of morphine.

Dopamine (DA) and DA-mimetics (apomorphine, midantan, piribedil) have a dual effect on Na, K-ATPase of the rat brain striate synaptosomes: activating at micromolar concentrations and inhibitory at higher concentrations (less than or equal to 30 microM). In the presence of Ca2+ (1 mM EGTA + 2.5 mM Ca2+) DA activating effect completely disappears and the inhibitory effect becomes even more pronounced. In the presence of cAMP (50 microM) which has no effect of its own on Na, K-ATPase, DA activation maximum is shifted towards lower concentrations, and the inhibitory effect remains unchanged. The above mentioned effects of DA persist in the presence of ouabain (1 mM), i.e. during measuring of Na, K-ATPase activity by an "ouabain" method, with DA activation maximum shifted towards higher concentrations.