Biomedical subjects
Publications and source records attributed to L Tóthfalusi.
After oral- and maxillo-facial surgical interventions both Apranax and Cataflam proved to be satisfying against pain. Though there is no difference in the kinetics of the effect, we found Apranax more effective to relieve postoperative pain. Besides the fast elimination of pain the medicine significantly mitigate the symptoms of inflammation.
Nonlinear regression algorithms were compared by Monte-Carlo simulations when the measurement error was dependent on the measured values (heteroscedasticity) and possibly contaminated with outliers. The tested leastsquares (LSQ) algorithms either required user-supplied weights to accommodate heteroscedasticity or the weights were estimated within the procedures. Robust versions of the LSQ algorithms, namely robust iteratively reweighted (IRR) and least absolute value (LAV) regressions, were also considered. The comparisons were based on the efficiency of the estimated parameters and their resistance to outliers. Based on these criteria, among the tested LSQ algorithms, extended least squares (ELSQ) was found to be the most reliable. The IRR versions of these algorithms were slightly more efficient than the LAV versions when there were no outliers but they provided weaker protection to outliers than the LAV variants.
High affinity 3H-paroxetine and 3H-imipramine binding sites were simultaneously studied in platelets of 29 untreated patients with panic disorder and 12 healthy controls. The maximum number of binding sites (Bmax) was found to be significantly lower in the panic patients compared to the controls using either ligand. No difference in the Kd values between the groups of subjects was found. The disturbance of serotonin neurotransmission in panic disorder--decrease in Bmax values--may be either a consequence or a reason of serotonergic dysfunction.
1. [3H]Noradrenaline ([3H]NA) release from the isolated main pulmonary artery of the rabbit has been measured in the presence of uptake blockers (cocaine, 3 x 10(-5) M, and corticosterone, 5 x 10(-5) M) and after blocking the monoamine oxidase enzyme by pargyline (1.2 x 10(-4) M). 2. In normal Krebs solution Mn2+ (2 mM) significantly inhibited both [3H]NA release (approximately 80%; P < 0.001) and the contraction following 2 Hz field stimulation. 3. In Ca(2+)-free, EGTA (1 mM)-containing solution, the Na+ pump was inhibited by removal of K+ from the external medium. In Na+ pump-inhibited arteries, 2 mM Mn2+ (free Mn2+, 1 mM) increased the spontaneous release of [3H]NA according to the time of Na+ loading. TTX (10(-7) M) did not inhibit significantly the Mn(2+)-induced [3H]NA release from Na(+)-loaded preparations (percentage inhibition, approximately 24; P > 0.30). 4. Without Na+ loading (Ca2+ free, EGTA alone), Mn2+ failed to promote 3H release from arteries. 5. With constant Na+ loading (120 min 'K(+)-free' perfusion in Ca(2+)-free, 1 mM EGTA-containing solution), the release of 3H was also directly dependent on free Mn2+ concentration (0.2, 0.6 and 1 mM). 6. The Mn2+ (2 mM; free Mn2+, 1 mM)-induced 3H release from Na(+)-loaded nerves (120 min 'K(+)-free', perfusion) was further enhanced, when external Na+ was simultaneously reduced from 139.2 to 26.2 mM (choline+ or sucrose substitution). 7. Diphenylhydantoin (DPH, 10(-4) M) significantly reduced the Mn(2+)-evoked 3H release (approximately 44%; P < 0.02) when it was present during 'K(+)-free', perfusion. 8. Mn2+ was ineffective in releasing 3H if the Na+ pump was previously reactivated by readmission of K+ to Na(+)-loaded arteries. 9. It is concluded that in Ca(2+)-free solution Mn2+ releases neurotransmitter in a manner which depends on the degree of loading with internal Na+. The results suggest this depends at least partly on a block of Ca2+ efflux.
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The effects of Trelibet (EGYT-475, N-benzyl-piperazine-picolinyl-fumarate) and its active metabolite (EGYT-2760, N-benzyl-piperazine) on the serotoninergic responses of rat stomach fundus were investigated and compared with those of MCPP (m-chlorophenyl-piperazine) which is the common metabolite of the arylpiperazine antidepressants Trazodone and Etoperidone. The contraction inhibitory potencies of the agents were determined on the equipotent contractions (EC50) to serotonin (5-HT) and prostaglandin F2 alpha (PGF2 alpha). Isotonic contractile responses to 5-HT were not affected by EGYT-475, however, both EGYT-2760 and MCPP produced concentration related and reversible inhibition of the serotoninergic responses. The IC50 values for EGYT-2760 and MCPP were 40.5 +/- 7.5 mumol/l and 125 +/- 35 nmol/l, respectively. The inhibition was selective for the serotoninergic responses, as the equipotent responses to PGF2 alpha were not affected. EGYT-2760 and MCPP displayed not only 5-HT antagonistic, but also partial agonistic activities on the rat fundus preparation. Maximum contractile response of the fundus preparation to MCPP was approximately 25%, to EGYT-2760 was 10% of the maximum response to 5-HT.
A normal cell count as well as normal CSF pressure levels were found in both classic and common migraine patients during and between attacks. Total protein content was significantly lower in the migraine patients than in the controls, but no changes were found in the CSF protein fractions. The CSF 5-hydroxyindoleacetic acid level of the migraine patients proved to be higher than in the controls, whereas the homovanillic acid concentration was within the control limits.
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We studied the mode of action of N-benzyl-piperazine-picolinylfumarate (EGYT-475) and of its metabolite N-benzyl-piperazine (EGYT-2760) in CFY rats. It was found that EGYT-475 had no uptake-inhibitory effect but EGYT-2760 inhibited the high-affinity uptake of 3H-noradrenaline, 3H-dopamine and especially that of 3H-serotonin both in vitro and ex vivo. Neither of the two compounds changed the serotonin turnover. Only EGYT-2760 evoked hyperthermia in rats at a high ambient temperature (28 degrees C). This effect was abolished by cyproheptadine but not by amitriptyline. EGYT-2760 antagonized serotonin-induced contractions of the stomach fundus but it was inactive in inhibiting the serotonin-induced platelet aggregation. Our results suggest that EGYT-2760, an active metabolite of EGYT-475, has a central serotoninomimetic action which involves 5-HT uptake-inhibition and 5-HT1 receptor agonistic effect.
Complex pharmacological effect of l-deprenyl cannot be explained by its MAO-B inhibitory action only. In contrast to other parent MAO inhibitors (J-512, J-516, LK-63, U-1424) l-, and d-deprenyl inhibit the hypothalamic noradrenaline and striatal dopamine (DA) reuptake without influencing the uptake of serotonin, both in rat and in human brain. Long-term treatment 19 x 0.25 mg/kg or 0.5 mg/kg, sc with l-deprenyl elicits 37 +/- 2.8 and 43 +/- 3.2% inhibition, respectively, of DA reuptake capacity in the rat striatal cell-free homogenate. To compare the potencies of deprenyl isomers on DA and DOPAC levels of rat striatum drugs were given 0.25, 2 and 8 mg/kg ip and their effects measured 4 and 48 h after treatment. DA content was increased only by 8 mg/kg d-deprenyl 4 h after its injection, but DOPAC level was decreased by both isomers. After 48 h, actions of d-deprenyl terminated but the effect of l-deprenyl was still present.
Platelets of migraine patients showed abnormal behavior such as hyperaggregability and reduced monoamine oxidase activity (MAO). We measured the MAO activity, serotonin (5-HT) content and release, adenosine diphosphate (ADP)-induced aggregation, and the prostacyclin (PGI2) antiaggregatory effect using the same sample of platelets from migraine patients to find out if these characteristics are intercorrelated. A significant correlation between MAO activity and sensitivity to PGI2 was found.
Deprenyl is a selective, irreversible inhibitor of monoamine oxidase type-B (MAO-B). In prolonged treatment (0.05-0.25 mg/kg, sc daily) in spite of the irreversible blocking, selective inhibition pattern of MAO was maintained. 14C-Deprenyl is well absorbed after oral or subcutaneous administration and penetrates rapidly to the central nervous system. When it is given intravenously its highest brain concentration is reached within 30 sec but radioactivity rapidly disappears from the central nervous system. Deprenyl is metabolized to amphetamine and methylamphetamine in rats without producing a remarkable sign of psychostimulant activity. This could partly be due to the distribution properties of deprenyl e.g. low detectable level of radioactivity in the brain after 1-2 min and partly to the fact that from (-) -deprenyl (-) -amphetamines, which have less psychostimulant activity than the (+) -isomere, are formed.