Effect of Carnosine in Experimental Arthritis and on Primary Culture Chondrocytes.

Carnosine's (CARN) anti-inflammatory potential in autoimmune diseases has been but scarcely investigated as yet. The aim of this study was to evaluate the therapeutic potential of CARN in rat adjuvant arthritis, in the model of carrageenan induced hind paw edema (CARA), and also in primary culture of chondrocytes under H2O2 injury. The experiments were done on healthy animals, arthritic animals, and arthritic animals with oral administration of CARN in a daily dose of 150 mg/kg b.

Synthesis and pharmacological evaluation of novel potential ultrashort-acting beta-blockers.

The basic relationship between chemical structure and pharmacological activity of eight newly developed potential ultrashort-acting beta-adrenergic blockers was evaluated. The compounds studied are derivatives of arylcarbonyloxyaminopropanols and were prepared by four-step synthesis. All the compounds evaluated showed weak antiisoprenaline (beta-adrenergic receptor blocking) activity and antiarrhythmic (antiouabain) activity.

[Anti-inflammatory activity of (o-cresotinate) copper and zinc aquacomplexes].

Using rat paw dextran-induced and carrageenan-induced edemas, the antiedematous activities of monohydrate of the diaquatetrakis(o-cresotato)dicopper(II) complex (CuoC) and the diaquabis(o-cresotato)zinc(II) complex (ZnoC) were assayed plethysmometrically. Dihydrate of the diaquabis(salicylato)copper(II) complex (CuS) and the diaquabis(salicylato)zinc(II) complex (ZnS) were used as the standards of comparison. All compounds were administered i.

[Anti-inflammatory activity of copper and zinc p-cresol dihydrate].

Using rat paw dextran-induced and carrageenan-induced edemas, the antiedematous activities of dihydrate of diaquatetrakis(p-cresotato)dicopper(II) complex (CupC) and diaquabis(p-cresotato)zinc(II) complex (ZnpC) were assayed plethysmometrically. Dihydrate of diaquabis(salicylato)copper(II) complex (CuS) and diaquabis(salicylato)zinc(II) complex (ZnS) were used as standards of comparison. All compounds were applied i.

[Preparation and antiinflammatory activity of selected aqua-(aryloxyacetate) zinc complexes].

Mononuclear aqua(aryloxyacetato)zinc(II) complexes of the composition [Zn(H2O)2(ROCH2COO)2] (R = phenyl, o-, m-, p-tolyl) were prepared as potential anti-inflammatory agents. The results of elemental analysis and parameters of IR spectra allow to classify the above-mentioned compounds to the group of carboxylatozinc(II) complexes with a distorted octahedral structure. They were assayed in rat paw carrageenan-induced edema and antiedematous effects were compared to those of free acids.

[Anti-inflammatory activity of (cresoxyacetate)copper complexes].

In groups of mononuclear aqua(cresoxyacetato)copper(II) complexes of the composition [Cu(ROCH2COO)2(H2O)n] (R= 2- and 3-methylphenyl, n = 2; 4-methylphenyl, n = 3) and binu- clear phenazone(o-, m-, p-cresoxyacetato)copper(II) complexes of the composition [Cu2(ROCH2COO)4(phz)2] the anti-inflammatory activity was assayed in rat paw carrageenan-induced edema. The effects of the complexes were compared with each other and with those of the free acids. Salicylic acid and its cupric salt (tetrahydrate) were used as standards of comparison.

[Antiedema activity of selected compounds with a gallate skeleton].

Using rat paw dextran-induced and carrageenan-induced edemas, the anti-inflammatory activity of gallic acid (I), triacetylgallic acid (II) and monohydrate copper(II) triacetylgallate (III) was assayed. All compounds tested were applied i.p.

[Antiedematous activity of certain arylcarboxylate copper aquacomplexes].

Using rat paw carrageenan edema, the anti-inflammatory activity of nine selected arylcarboxylatocopper(II) aquacomplexes of the general composition Cu(RCOO)2.nH2O, where R represents 2-hydroxy-Y-methylphenyl, Y = 3 (n = 1.5), 4 (4) or 5 (2); 2-hydroxy-3,6-dimethylphenyl (n = 4); 2,5-diacetoxyphenyl (1); 2-methoxy-(1) and 4-methoxyphenyl (3); 2-furyl (3) and 2-thienyl (1), was assayed and compared to that of the free acids.

[Pharmaco-toxicologic evaluation of newly synthesized analogs of propafenone].

The basic pharmacological evaluation of five analogues of propafenone was the aim of the present paper. Antiarrhythmic activity of the compounds at 10(-5) mol.kg-1 was established in guinea-pigs using experimental arrhythmias induced by ouabain and aconitine.

[Anti-inflammatory activity of aqua-bis(2,Y-diacetoxybenzoate)-copper complexes (Y=4, 5 or 6)].

In a group of binuclear copper (II) complexes of the composition [Cu2(RCOO)4(H2O)2] (R = 2,4-diacetoxyphenyl (I), 2,5-diacetoxyphenyl (II) and 2,6-diacetoxyphenyl (III)), the anti-inflammatory activity was assayed in rat paw carrageenan-induced edema. Copper (II) salicylate tetrahydrate (IV) and salicylic acid were used as standards for comparison. All compounds were applied i.

[Antiexsudative activity of (methylsalicylate)copper-water compounds].

Using rat paw dextran edema, the antiexudative activity of the complexes of the composition Cu(RCOO)2.nH2O--R represents 2-hydroxy-Y-phenyl: Y = 3 (n = 1,5), Y = 4 (4), Y = 5 (2) or 2-hydroxy-3,6-dimethylphenyl (n = 4)--and of the corresponding uncomplexed acids was assayed. Salicylic and acetylsalicylic acids and their Cu(II) salts were used as standards of comparison.

Carbamate analogues of tocainide.

A series of the new aminoalkyl esters of chlor-, methyl- and alkoxy carbanilates was synthesized. All the compounds prepared were found to exhibit antiarrhythmic activities comparable with those of mexiletine.

[Preparation and pharmacologic profile of derivatives of alkoxyphenylcarbamic acid with potential effects on the cardiovascular system].

In a systematic study of the relationship between the chemical structure and beta-adrenolytic activity, eleven derivatives of the 4-alkoxysubstituted phenylcarbamic acids were prepared. The beta-adrenolytic efficiency of the compounds was studied in the isolated spontaneously beating guinea-pig atria and expressed as pA2 values against isoprenaline tachycardia. Negative chronotropic and antidysrhythmic activity were also evaluated.

[Anti-pyretic activity of aqua-(diacetoxybenoate)-copper complexes].

The antipyretic activity of binuclear (diacetoxybenzoato)-copper(II) aquacomplexes [Cu2(2,Y-DAB)4(H2O)2] (Y = 4 and 5) as well as cupric acetylsalicylate [Cu2(AcSal)4] was assayed in a rabbit model of endotoxin-induced fever. The complexes and uncomplexed carboxylic acids (administered i.p.

The influence of carbamate local anesthetics on the occurrence of experimental gastric ulcers.

Evaluation of the antiulcer effects of a series of 2-piperidineethylesters of o-alkoxy-substituted phenylcarbamic acids were performed using two experimental models of gastric ulcers, e.g. induced by stress or by ligation of the pylor.

[Changes in myocardial sensitivity after sudden with withdrawal of calcium channel blockers].

Our previous experiments have suggested that besides the receptor cont and/or sensitivity a decrease of intracellular calcium level significantly participates in the mechanism of beta-blocker withdrawal 'rebound' phenomenon. This suggestion initiated studies in which possible changes in myocardial responsibility to cardioactive drugs were investigated in the condition of withdrawal of treatment with calcium entry blockers. The results showed increased cardiotoxicity of ouabain, aconitine and CaCl2, as well as an increased response of the heart to isoprenaline 24 hours after sudden cessation of treatment with verapamil (2 mg.

[Anti-inflammatory and antipyretic activity of aqua-dihydroxybenzoate copper complexes].

Using screening methods, the anti-inflammatory and antipyretic activities of mononuclear otahedral complexes [composition:Cu(2,YDHB)2.H2O;dihydroxybenzoate ion - DHB; Y(n)-4(8).5(4) and 6(8)] and the corresponding carboxylic acids were studied.

[Local anesthetics. 90. Asymmetric dibasic alkyl esters of alkoxyphenylcarbamic acids].

The synthesis of 24 compounds belonging to the group of dibasic substituted alkoxy phenyl carbamic acids is described. The compounds are characterized by relatively low acute toxicity and good local anaesthetic as well as antiarrhythmic activity.

Pharmacological properties of a new local anaesthetic, carbisocaine.

During the systematic analysis of the relationship between chemical structure and local anaesthetic activity of basic esters of alkoxyphenylcarbamic acids, the diethylamino-isopropylester of 2-heptyloxyphenylcarbamic acid (carbisocaine) was synthesised and later extensively studied. This drug has been shown to be as active as procaine in skin anaesthesia in molar concentrations 416 times lower, and in corneal anaesthesia the drug parallels the standard agent cocaine in molar concentrations 251 times lower. The high relative local anaesthetic potency of carbisocaine and its low subcutaneous toxicity prompted wider pharmacological investigations in which the effects of carbisocaine on the central nervous system and the circulation were studied.