The biodegradation of fullerene C by myeloperoxidase.

It is shown for the first time that the mammalian enzymes can cause the degradation of the C60 fullerene molecules. This biodegradation is caused by the action of а hypochlorite generated neutrophil enzyme myeloperoxidase of fullerene molecule and leads to the loss of the topology of the fullerene core.

Enhanced brain penetration of hexamethonium in complexes with derivatives of fullerene C60.

The present report describes development of hexamethonium complexes based on fullerene C60. Hexamethonium has a limited penetration into CNS and therefore can antagonize central effects of nicotine only when given at high doses. In the present studies conducted in laboratory rodents, intraperitoneal administration of hexamethonium-fullerene complexes blocked effects of nicotine (convulsions and locomotor stimulation).

[Effect of different water-soluble forms of the fullerene C60 on the metabolic activity and ultra-structure of cells in culture].

In view of contradictory data on the toxicity of fullerenes for live organisms we studied the effect of water-soluble complexes of C60 with N-polyvivyl-pirrolidone (C60/PVP) and gamma-cyclodextrine (C60/gamma-CD) on MA-104 cells in culture. Both complexes proved to be non-toxic for cultured cells in the dark in wide range of concentrations. Both complexes provoke changes of cellular ultra-structure which reflect the enhancement of metabolic activity.

[Effect of polymer carrier origin and physical state on fullerene C60 phototoxicity in vitro].

Biological effects of water-soluble inclusion complexes of fullerene C60 with poly(vinyl pyrrolidone) (C60/PVP) and gamma-cyclodextrin (C60/g-CD) as well as solid C60 (C60-coated surface) on cell viability have been studied in vitro. It is established that both inclusion complexes (in a broad range of concentrations) and solid fullerene coatings are nontoxic in the dark for the cell of all lines tested. In contrast, under intense UV illumination, the C60/PVP complex reliably protected test cells from the UV radiation damage, whereas the C60/g-CD and fullerene-coated surface exhibited pronounced phototoxicity.

[Effect of fullerene C60-polyvinilpyrrolidone complexes on influenza virus reproduction].

The capacity of water-soluble complexes of fullerene C60-polyvinylpyrrolidone to inhibit the replication of influenza viruses was studied. In contrast to remantadine, these complexes inhibit the replication of both A and B viruses (including the remantadine-resistant strains). The complexes inhibit influenza virus replication at all stages of replication cycle.

Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid.

Three amino-alkylated derivatives of the naturally occurring excitatory amino acid (EAA) receptor agonist ibotenic acid (Ibo) have been synthesized and tested pharmacologically. N-Methyl-Ibo (1a) and N-ethyl-Ibo (1b) were shown to be agonists at NMDA receptors (EC50 = 140 and 320 microM, respectively), though with activities considerably lower than Ibo (EC50 = 9.6 microM).

Excitatory amino acid receptor antagonist kynurenic acid attenuates rewarding potential of morphine.

The effect of the non-selective antagonist of excitatory amino acid receptors kynurenic acid (50, 100 and 150 mg/kg, i.p.) on morphine-derived reward was studied in rats.

[The effect of N-methyl-D,L-aspartic acid on the nociceptive reaction of mice].

Intraperitoneal NMDLA was pharmacologically studied in mice for effects by using the hot-plate test. The agent given in a subconvulsive dose of 50 mg/kg showed a biphasic action: 5 minutes after administration there was hyperalgesia (Phase I) followed by hypoalgesia (Phase II) 15 minutes later. The effects of phencyclidine, ketamine, morphine, naloxone, bromocriptine and isradipine on NMDLA's analgetic action were also examined.

[Effects of N-phthalamoyl-L-glutaminic acid, a selective agonist of NMDA receptor, on binding of 3H-L-glutamate with synaptic membranes of the hippocampus].

In the present investigation the interaction of a novel selective NMDA receptors agonist, N-phthalamoyl-L-glutamic acid (PhGA), with the synaptic membranes preparation of human hippocampus was examined against NMDA. It was established that there are two binding sites of 3H-L-Glu, Kd1 = 0.35 +/- 0.

Excitatory action of some aspartate- and glutamate-containing dipeptides after intracerebroventricular injection in mice.

The effects of some dipeptides, analogues of N-acetyl-alpha-L-aspartyl-L-glutamate, were studied after i.c.v.

A novel selective NMDA agonist, N-phthalamoyl-L-glutamic acid (PhGA).

Ionic currents elicited by N-phthalamoyl-L-glutamic acid (PhGA) were investigated on freshly isolated hippocampal neurons with the whole-cell voltage clamp and concentration clamp techniques. PhGA elicited desensitizing inward currents in Mg(2+)-free salines only in the presence of glycine. The dose-response relationship for PhGA was close to a Langmuir isotherm with Kd = 3.

[Comparative characteristics of the membrane mechanisms of the action of fenamine and its derivatives on the ion channels of isolated mollusk neurons].

Phenamine (10(-12)-10(-5) M/l) increased by 20-60 per cent the input (sodium and calcium) currents (Iin), the output slow potassium (Ikm) and fast potassium (Ikb) ones, and decreased the currents in higher concentrations. The volt-ampere characteristics of the membrane (VAC) and the curves of stationary inactivation (CSI) shifted along the potentials axis. The phenamine analogue IEM 1365 only decreased the currents leaving the VAC and CSI unaltered.

[Mnemonic effects of substituted amides of imidazole-4(5)-carboxylic acid in rats].

The effects of four derivatives of imidazole-4(5)-carboxylic acid on the formation and extinction of the conditioned drinking reflex and the preservation of the conditioned response of passive avoidance after electroconvulsive shock or mechanic craniocerebral injury were studied during experiments on rats. N-methylamide of imidazole-4(5)-carboxylic acid exhibited the greatest psychostimulant and antiamnestic activity. Addition of beta-phenylisopropyl radical to NH2-group resulted in the appearance of depressant properties.

[Prodrugs: goals, principles and outlook].

The review covers the principles of creation of prodrugs as a chemical system for delivering drugs to targets. It presents the strategy of prodrug design and describes the main approaches to creation of prodrugs for drugs of different classes: antibiotics, anti-inflammatory and antitumour agents, corticosteroids, agents of the central action, etc.

[Experimental research on the action of isoptin and alkylenediamine derivatives on the aggregation capacity and the membrane-bound calcium level of thrombocytes].

It was found in experiments on rabbit platelets that isoptin and derivatives of N,N'-di(beta-phenylisopropyl)polymethylene diamines produce a dose-dependent decrease of the platelet aggregation activity. The effect correlates with a lowering of membrane-bound calcium level in platelets as shown by the fluorescent technique with the use of chlortetracycline probe. The results obtained demonstrate that the derivatives of alkylenediamines significantly suppress platelet aggregation and block membrane-bound calcium at the lower concentrations than those of isoptin.