Synthesis and structure-activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: a novel series of 5-HT(2A/2C) receptor antagonists. Part 2.

Following the programme started at Janssen Research Foundation searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of a series of substituted 2-(Dimethylaminomethyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives. The 5-HT(2A), 5-HT(2C) and H(1) receptor affinities as well as the mCPP antagonistic activity of the compounds synthesised is described.     

Determination of antithrombocyte antibodies in the blood serum of patients with idiopathic thrombocytopenic purpura by an immunoenzyme method

Enzyme-linked immunosorbent assay (ELISA) was developed for determination of serum antiplatelet antibodies. Platelets obtained from healthy donors of blood group 0(1) were washed off plasma and sedimented on the bottom of microtest wells. After washing off unattached platelets and blocking of plastic with albumin platelets were incubated with sera under investigation and binding of serum antibodies was detected using antihuman immunoglobulin antibodies conjugated with peroxidase. Ten patients with idiopathic thrombocytopenic purpura (ITP). 1 patient with systemic lupus erythematosus. 1 patient with red blood cell aplasia and 9 healthy donors (negative control) were studied by ELISA. Serum antibodies which effectively bound to platelets were detected in 5 patients with ITP, in patient with lupus erythematosus and in patient with red blood cell aplasia.     

Effector modeling of the action of ligands of GABA-receptor complex. Functional interaction of the hypothetic alcohol receptor with other subunits of the complex

The types of the interaction of the pharmacological effects of ethanol and barbiturate antagonists--picrotoxin, bemegride and corasol--were determined. The effect of ethanol was determined as competitive--for the convulsant effects of bicuculline, and non-competitive--for the effects of thiosemicarbazide. The indices of the anticonvulsant effects of n-aliphatic alcohols were compared. It is suggested that n-aliphatic alcohols alter the functional status of the supramolecular GABA-receptor channel ensemble. The pharmacological properties and the elements of the structural similarity of picrotoxin and n-propanol (the presumptive ligand of the GABA-receptor channel ensemble) are discussed.     

Intrinsic nerves of the pectoralis major and minor in man

In the human intraorganic nerves of the thoracic muscles amyelin fibers make 62% and myelin ones--38%. In transversal sections ultrastructure of the myelin and amyelin fibers varying in their diameters has been studied. In the myelin and amyelin fibers the amount of various organells is not equal: in the amyelin fibers the arrangement density of microtubules is greater than that of neurofilaments, there is a reverse dependence between the amount of the microtubules and the neurofilaments on the one hand, and the fibrilar diameter, on the other hand. In the myelin fibers with the increasing diameter, the amount of the neurofilaments increases, while that of the microtubules decreases.     

The action of an enzymatically stable Leu-enkephalin analog on the prostanoid content in the myocardium under stress- and adrenaline-induced damage

The protective action of enzymatically stable analogue of Leu-enkephalin (D-ala-2-leu5-arg6), injected intraperitoneally, in the course of stress- and epinephrine induced myocardial damage was demonstrated in animal (129 white rats) experiments. Two effect of enkephalin were sufficient for the cardiac protection: enkephalin-stimulated prostacyclin biosynthesis and simultaneous inhibition of thromboxane production.