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Kalman Toth

Publications and source records attributed to Kalman Toth.

22 records · Page 2Linked to original sources
PubMed2002

The antinociceptive effect of intrathecal kynurenic acid and its interaction with endomorphin-1 in rats.

Kynurenic acid as an endogenous ligand antagonizes all types of ionotropic glutamate receptors, with preferential affinity for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor. The purpose of the present study was to investigate the antinociceptive potency of continuously administered kynurenic acid on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal test in awake rats. The possible interaction between kynurenic acid and the endogenous mu-opioid receptor agonist peptide, endomorphin-1, was examined in the same set-up. Kynurenic acid at the higher doses (1-4 microg/min) significantly decreased the thermal hyperalgesia and increased the paw withdrawal latencies on the non-inflamed side. These doses were also associated with motor impairment on both sides. Low doses of kynurenic acid (0.01-0.1 microg/min) potentiated, but did not prolong, the antinociceptive effect of endomorphin-1 (0.1-1 microg/min) on the inflamed side. There was no sign of motor impairment during the combined treatment. These findings demonstrate that the combination of low doses of these two endogenous ligands provides effective and well-controlled antinociception without side effects.

Analgesics↗
PubMed2002

2,2,5,5-Tetramethylpyrroline-based compounds in prevention of oxyradical-induced myocardial damage.

Reactive oxygen species have been known to play a major role in a wide variety of pathophysiologic processes. A new compound, H-2545, based on a 2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide structure, has been reported to exhibit antiarrhythmic function as well as favorable antioxidant properties. Studies were performed in an isolated rat heart model to measure the efficacy of H-2545 and its metabolite, H-2954, in preventing ischemia-reperfusion and hydrogen peroxide-induced oxidative myocardial damage: lipid peroxidation, protein oxidation, activity of respiratory complexes, NAD, and high-energy phosphate metabolism. The cardioprotective effects of examined compounds were compared with that of a well-known water-soluble vitamin E analog, Trolox. To determine whether the antioxidant property of H-2545 is due to the pyrroline ring, the scavenger effects of mexiletine and HO-2434 (mexiletine substituted with a pyrroline group) were compared. The results showed that H-2545 decreased significantly the ischemia-reperfusion-induced thiobarbituric acid reactive substance (TBARS) formation, the protein oxidation and ssDNA break formation in perfused rat hearts. H-2545 decreased the NAD loss in postischemic hearts. The activity of respiratory complexes, myocardial energy metabolism, and functional myocardial recovery were also improved during reperfusion by adding H-2545 to the perfusion medium. H-2954 exerted significantly lower protection against ischemia-reperfusion-induced myocardial injury than H-2545, and it was comparable to that of Trolox. Both H-2545 and H-2954 are highly effective against H O -induced oxidative myocardial cell damage. The findings show that substitution of mexiletine with a 2,2,5,5-tetramethyl-pyrroline group (HO-2434) increased its antioxidant and cardioprotective effects. In conclusion, these results suggest that sterically hindered pyrroline derivatives accumulating in membranes can be highly effective at preventing oxidative myocardial cell damage.

Animals↗
PubMedDate not supplied

In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine.

Oxygen-free radicals play an important role in several physiologic and pathophysiologic processes. In pathologic circumstances, they can modify and damage biologic systems. Because oxygen-free radicals are involved in a wide range of diseases (cerebrovascular, cardiovascular, etc.), scavenging these radicals should be considered as an important therapeutic approach. In our in vitro study, we investigated the antioxidant capacity of three drugs: pentoxiphylline (Sigma Aldrich, St. Louis, MO, USA) piracetam (Sigma Aldrich), and vinpocetine (Richter Gedeon RT, Budapest, Hungary). Phenazine methosulphate was applied to generate free radicals, increasing red blood cell rigidity. Filtration technique and potassium leaking were used to detect the cellular damage and the scavenging effect of the examined drugs. According to our results, at human therapeutic serum concentration, only vinpocetine (Richter Gedeon RT) had significant (p < 0.01) scavenging activity with a protective effect that increased further at higher concentrations. Pentoxiphylline (Sigma Aldrich) and piracetam (Sigma Aldrich) did not have significant antioxidant capacity at therapeutic concentrations, but increasing their concentrations (pentoxiphylline at 100-times, and piracetam at 10-times higher concentrations) led to a significant (p < 0.01) scavenger effect. Our findings suggest that this pronounced antioxidant effect of vinpocetine and even the milder scavenging capacity of pentoxiphylline and piracetam may be of value in the treatment of patients with cerebrovascular disorders, but merits further investigations.

Antioxidants↗