[The action of ionotropic glutamate receptor channel blockers on effects of sleep deprivation in rats].

The action of non-competitive glutamate receptor antagonists on the effects of sleep deprivation has been studied on Krushinskii-Molodkina rats having an inherited predisposition to audiogenic seizures and Wistar rats deprived to this respond. Two types of glutamate receptor open channels blockers were used: the selective blockers of NMDA-receptors (memantine and IEM-1921) and blockers of mixed type, impacting both on the NMDA- and presumably Ca(2+)-permeable AMPA/kainate receptors (IEM-1754 and IEM 1925). Rats were subjected to 12 hours long sleep deprivation.

[The ability of NMDA glutamate receptor blockers to prevent a pentylenetetrazole kindling in mice and morphological changes in the hippocampus].

We investigated in mice the relationship between convulsions and morphological changes of hippocampal neurons that arise in the development of pentylentetrazol (PTZ)-induced kindling. The kindling was caused by of 35 mg/kg PTZ i.p.

[The effect of ionotropic glutamate receptor antagonist on pentylenetetrazole-indused seizures in Krushinsky-Molodkina rats].

Krushinsky-Molodkina (KM) rats exhibit inherited susceptibility to audiogenic seizures and auditory stimuli induce generalized tonic-clonic seizures that resemble human epilepsy. The aim of this study was to compare the neurological manifestations of pentylenetetrazole (PTZ)-induced seizures in Wistar and KM rats to clarify the contribution of inherited susceptibility to audiogenic seizures, and to assess the anticonvulsant activity of NMDA receptor blockers memantine and IEM-1921 (1-phenylcyclohexylamine) in the PTZ-induced seizure model in KM rats. KM rats exhibited increased seizure severity relative to Wistar rats, and the death of KM rats was observed in 2.

[Effects of ionotropic glutamate receptor channel blockers ON sleep-waking organization in rats].

The effects of non-competitive glutamate receptor antagonists on sleep-waking organization have been studied on Krushinskii-Molodkina rats having an inherited predisposition to audiogenic seizures and Wistar ones which are resistant to this action of sound. Two types of blockers of glutamate receptor open channels were used: selective blockers of NMDA receptors (memantine and IEM-1921) and blockers of mixed type, impacting both on the NMDA and Ca-permeable AMPA/ kainate receptors (IEM-1754 and IEM 1925). During the first 3 hours after administration of these glutamate antagonists the total or partial deprivation of fast-wave sleep was provoked.

[Effects of ionotropic glutamate receptor channel blockers on the development of audiogenic seizures in Krushinski-Molodkina rats].

The action of noncompetitive blockers of glutamate receptors has been investigated on Krushinski-Molodkina rats genetically-prone to audiogenic seizures. The selective blockers of NMDA receptor channels, memantine and IEM-1921, and their dicationic homologues, IEM-1925 and IEM-1754, capable of blocking in varying degrees both NMDA and Ca-permeable AMPA receptor channels, were studied. The drugs were injected intramuscularly to rats with the different time intervals (30 min, 1, 2 or 3 hours) before sound signal.

[Effects of memantine on convulsive reactions and sleep-waking cycle in Krushinskiĭ-Molodkina strain rats with the inherited predisposition to audiogenic convulsions].

Krushinskii-Molodkina strain rats have an inherited predisposition to audiogenic convulsions and are used as a natural animal model in the anticonvulsive drugs studies. We have investigated whether changes in the glutamatergic synaptic transmission are involved in the mechanism of audiogenic convulsions and functional organization of sleep-waking cycle observed in rats of this line. For this purpose Memantine, a selective uncompetitive blocker of NMDA receptors was used.

[Involvement of ionotropic glutamate receptors in the genesis of arecoline-induced tremor].

The muscarinic agonist arecoline (6 mg/kg, subcutaneously in mice) induced a long-lasting tremor. The inhibitory potency of non-competitive antagonists of ionotropic glutamate receptors has been studied. These antagonists are the derivatives of adamantane and phenylcyclohexyl.

[Mechanisms of blockade of glutamate receptors channels: the significance for structural and physiological investigations].

The mechanism of blocking effect of phenylcyclohexyl derivative, IEM-1925, on ionotropic glutamate receptors of the NMDA and AMPA types has been studied on the rat isolated brain neurons. The whole-cell configuration of patck clanp recording technique was used equilibrium conditions and -80 mV holding potential, the IEM-1925 manifests nonselective action on open channels of both receptors. However, the prominent differences in the mechanism of the blocking effect were revealed.

[Effects of blockade of ionotropic glutamate receptors on the development of pentylenetetrazole kindling in mice].

Effects of mono- and dicationic derivatives of adamantane and phenylcyclohexyl on the petyleneterazole-induced (35 mg/kg i. p.) kindling were studied in the experiments on mice.

[Role of NMDA and AMPA glutamate receptors in the mechanism of korazol-induced convulsions in mice].

The potency of mono- and dikationic derivatives of adamantane and phenylcyclohexyl to prevent seizures induced in mice by intraperitoneal administration of 80 mg/kg pentylenetetrazol (corazol), was studied. Monocationic derivatives of phenylcyclohexyl, being the selective channel blockers of NMDA glutamate receptors, as well memantine and MK-801 in micromolar concentrations, prevented both clonic and tonic components of corazol-induced convulsions. Their dicatonic derivatives which are channel blockers of NMDA and AMPA types of glutamate receptors, failed to prevent clonic seizures but at submicromolar concentrations prevented the tonic extensions provoked by corazol.

[Comparison of the anticonvulsant activity of organic mono- and di-cations and their potential to inhibit NMDA and AMPA glutamate receptors].

Effects of mono- and dicationic derivatives of adamantine and phenylcyclohexyl were studied on: (i) open channels of NMDA and AMPA glutamate receptors in the experiments on the isolated rat brain neurones, and (ii) convulsions induced by intraventricular injections of NMDA or kainate in mice. Monocations inhibited the NMDA receptors in vitro and prevented convulsions induced by NMDA in vivo, but failed to affect both the AMPA receptors and kainite-induced convulsions. Dications (IEM-1754 and IEM-1925) revealed both anti-NMDA and anti-AMPA potency in vitro, were highly effective against kainite-induced convulsions and excelled monocations in preventing the NMDA-induced ones.

[Ion channel topography of the neuronal nicotinic acetylcholine receptor : pharmacochemical approaches].

Forty-three bisammonium ganglionic blockers were synthesized to study the structure of the ion channel of nicotinic acetylcholine receptor. The conformational parameters of these blockers were studied, and their effects toward the ganglionic transmission in situ on the sympathetic feline upper cervical ganglions and in vitro on the parasympathetic guinea-pig small intestine ganglions were determined. A model of the binding site for the bisammonium ganglionic blockers in the neuronal ion channel was proposed.

[Ability of novel non-competitive glutamate receptor blocking agents to weaken motor disorders in animals].

Action of mono- and dication derivatives of phenylcyclohexyl was compared with effects of known NMDA-antagonists memantine and dizocilpine. Seizures induced with the NMDA were effectively prevented both by mono- and dications, whereas against the kainate seizures dication alone was effective. Anticataleptic activity was much stronger in monocations, and the side effect of the substances under study on motor co-ordination was obviously weaker than in dizocilpine.

[Structural characteristics of ionotropic glutamate receptors revealed by channel blockade].

The topography of the channel binding site in glutamate receptors (AMPA and NMDA types of rat brain neurons, receptors of molluscan neurons and insect muscle), and in two subtypes of nicotinic cholinoreceptors (in frog muscle and cat sympathetic ganglion), has been investigated by comparison of the blocking effects of mono- and dicationic derivatives of adamantane and phenylcyclohexyl. The channels studied can be divided into two groups. The first one includes AMPA receptor and glutamate receptors of mollusc and insect, and is characterised by the absence of activity of monocationic drugs and the strong dependence of dicationic once on the internitrogen distance in the drug molecule.

[Glutamate receptor antagonists attenuate experimental catalepsy in rats].

A long-term akinesia induced by haloperidol used as an experimental model of catalepsy helped to reveal that a dicationic derivatives adamantane (IEM-1754) and phenylcyclohexyl (IEM-1925) exerted different degrees of inhibition of the haloperidol effect: the IEM-1754 proved to be not inferior to the most effective NMDA antagonist MK-801. A relatively low potency of the IEM-1925 may be due to its obvious equal effects both on the NMDA and the AMPA receptor channels. A good correlation between the anticataleptic effects of the glutamate antagonists and the NMDA receptor blocking activity, were found.

[The participation of glutaminergic transmission in the mechanism of movement disorders induced by reverse rotation in white mice].

Administration of MK-801 or IEM-1754 prevented akinesia in mice induced by reversing rotation, not less effectively than scopolamine. Quaternary adamantane derivative IEM-1857 was ineffective. IEM-1925 enhanced the locomotor disturbance induced by reversing rotation due, probably, to different spectrum of its antiglutamate action.

[The blockade of glutaminergic and cholinergic ion channels by adamantane derivatives].

It has been shown that a homologous series of adamantane derivatives of general structure Ad-CH2-N+H2-(CH2)5-N+R3, where Ad, adamantane, R varied from H (hydrogen) to t-Bu (tertiary butyl), blocks the open state of postsynaptic activated channels. In the presence of the drugs studied the decay of evoked cholinergic postsynaptic currents in frog neuromuscular junction could be fitted by two exponentials. However, the rate constants of interaction of blocker with channel did not depend on the R structure and membrane potential.

[Comparative research on synaptic transmission in the sympathetic ganglia of rabbits and frogs during acetylcholinesterase inhibition].

Organophosphorus inhibitor of acetylcholinesterase (AChE) armin (1 x 10(-6) M) induced a variety of pre- and postsynaptic effects resulting from the AChE inhibition and subsequent accumulation of acetylcholine (ACh) in the synaptic cleft. The intensity of postsynaptic effects (level of neuron depolarization, degree of action potential depression) was shown to be different in the ganglia of frog and rabbit. This could be explained by differences in the total amount of ACh released in response to nerve stimulation as well as at rest.

[Synaptic effects of nicotinic and muscarinic agonists in the sympathetic ganglia of the frog].

Superfusion of isolated frog sympathetic ganglia with nicotinic agonists (suberyldicholine, tetramethylammonium, DMPP), as well as with acetylcholine in the presence of atropine, caused short-term depolarization of a single ganglion cell and blockade of synaptic transmission. Muscarinic agonists (methylfurmethide, methyl dilvasen, acetylcholine) caused sustained depolarization which was not accompanied by transmission failure. Oxotremorine did not change membrane potential at concentrations up to 1.