Pharmacological characterization of the vasodilator effect of DF-100, a new pyridazino[4,5-b]indole, in vascular smooth muscle.

DF-100, i.e., 1-hydrazino-4-(3,5-dimethyl-1-pyrazolyl)-5H-pyridazino[4,5-b ]indole is a new pyridazino[4,5-b]indole derivative related to dihydralazine.

Antihypertensive and vasodilator effect of A-80b, a new pyridazino indole derivative.

The hypotensive and antihypertensive activities of a A-80b, a newly synthesized pyridazino[4,5-b]indole derivate were investigated in anaesthetized rats. In vitro studies were also done to examine the possible mechanism of its vasodilator action. A 80b (3-15 mg/kg i.

New indole and triazino[5,4-b]indol-4-one derivatives: synthesis and studies as inotropics and inhibitors of blood platelet aggregation.

New triazino[5,4-b]indol-4-one derivatives carrying amino groups in position 3 were synthetized and tested as inotropic agents and inhibitors of platelet aggregation. 2h, 2p, 5p, and 6g are the most active as inotropic agents. Compounds were tested as inhibitors of platelet aggregation induced by adenosine 5'-diphosphate (ADP) and arachidonic acid (AA) (guinea pig whole blood).

Quantitative structure-mutagenic activity relationships of triazino indole derivatives.

The mutagenicity of 3-(4'-benzylidenamino)-5H-1,2,3-triazin[5,4-b]-indol-4-one derivatives, new compounds with considerable platelet antiaggregating activity, was assayed with the Ames test using the Salmonella typhimurium strains TA97, TA98, TA100 and TA102. The adaptive least-squares method (ALS method) was used to carry out a quantitative structure-activity relationship (QSAR) analysis. Three equations, based on 10 congeners, were found for strains TA97, TA98 and TA100.

Bacterial mutagenic evaluation of a series of 4' substituted derivatives of 3-benzylidenamino-5H-1,2,3-triazin[5,4b]indol-4-one.

The mutagenicity of ten triazinoindole derivatives was studied in bacteria. The compounds form part of a 3-(4'-substituted-benzylidenamino)-5H-1,2,3-triazin[5,4-b]in dol-4-one series and differ in the physicochemical properties of the substituent at the 4' position of the benzylidenamino group: -H, -OH, -COOH, -OCH3, -COOCH3, -NHCOCH3, -C1, -NO2, -C6H5, and -OC6H5. They were tested in the TA97, TA98, TA100, and TA102 strains of Salmonella typhimurium, both with and without metabolic activation, using the preincubation procedure.

Detection of nephrotoxicity in cyclosporine-A amyotrophic lateral sclerosis patients by means of urinary cytology.

Exfoliative urinary cytology was used for two amyotrophic lateral sclerosis patients treated with 3 mg/kg/day cyclosporine (CsA) therapy in order to detect the onset of the nephrotoxic side-effects of the drug before the apparent deterioration of the patients' clinical condition. Of the two patients, only one showed clear morphological features of drug-related damage in a one year course of cyclosporine therapy, but these followed the increase in the serum kidney and liver laboratory parameters and did not prove useful for the early detection of nephrotoxicity. However, in this patient the renal damage was hallmarked by an increasing number of tubular cells or clusters of ill-defined renal cells in the urinary specimen, suggesting an ongoing tubular injury.

New 5H-pyridazino[4,5-b]indole derivatives. Synthesis and studies as inhibitors of blood platelet aggregation and inotropics.

Some fused 5H-pyridazino[4,5-b]indoles (7-10), substituted in positions 1 and 4 by hydrazine and/or amino groups, have been synthesized. These new compounds present a planar topography, a dipole with an adjacent acidic proton, and a basic hydrogen-acceptor site opposite the dipole. These compounds have some resemblance to carbazeram and other pyridazino agents with cardiotonic activity.

New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidine derivatives as diuretics.

New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidines 1 and 6,10-dihydro-5H-pyrido[3',2':5,6]pyrimido[2,1-c] [1,2,4]triazines 4 with 5-one, 5-thione or 5-hydrazono substituents and in some cases 1,2,3,4 or 8,9 hydrogenated are synthetized. The diuretic, natriuretic and kaliuretic activities of these compounds in Wistar rats at a dose of 24 mg/kg were estimated. A series of 24 possible derivatives of 1 and 4 possessing diuretic and saliuretic activities are investigated for structure-activity relationships in light of Fujita-Ban model.

Diuretic and hypotensive activities of 4-anilino derivatives of 2-methylthiopyrido[2,3-d]pyrimidines.

The synthesis of a series of 12 compounds referring to 4-anilino-2-methylthiopyrido [2,3-d]pyrimidines (1-12), and the results of a study of their diuretic, saliuretic and antihypertensive activities are reported. Most of this compounds showed significant diuretic activity at the dosage of 3-24 mg/kg. The 4-Anilino-2-methylthiopirido[2,3-d]pyrimidine 1 remained active to a dosage of 1 mg/kg.

Mutagenic evaluation of some triazino indoles using the Salmonella/mammalian microsome assay.

The mutagenicity of ethyl 1,2,3-triazino[5,4-b]indole-4-carboxylate N(3)-oxide (D3) and 2-chloroethyl 1,2,3-triazino-[5,4-b]indole-4-carboxylate N(3)-oxide (D4), heads of series of new products with considerable platelet antiaggregating and hypotensive activity, and their precursors 2-ethoxy-carbonylmethyl-1-methylindole-3-carboxylic acid (A3) and 2-(2-chloroethoxycarbonylmethyl)-1-methylindole-3-carboxylic acid (A4) were tested in four strains of Salmonella typhimurium (TA98, TA100, TA97 and TA102) using the standard plate incorporation technique. A3 and A4 were not mutagenic whereas D3 was mutagenic to all the strains and D4 was mutagenic to TA97, TA98 and TA100. The addition of 4 or 10% of S9 mix decreased the mutagenic activity of both compounds.

Selective thromboxane synthetase inhibitors and antihypertensive agents. New derivatives of 4-hydrazino-5H-pyridazino[4,5-b]indole, 4-hydrazinopyridazino[4,5-a]indole, and related compounds.

A series of new derivatives of 4-hydrazino-5H-pyridazino[4,5-b]indole (5) and 4-hydrazinopyridazino[4,5-a]indole (12) have been synthesized to investigate their activities as selective thromboxane synthetase inhibitors as well as antihypertensive agents. Several of the prepared compounds were found to be selective thromboxane synthetase inhibitors, in concordance with the Gorman model. The most potent were 8-(benzyloxy)-3,4-dihydro-4-oxo-5H-pyridazino[4,5-b]indole (3c) and 8-methoxy-4-hydrazino-5H-pyridazino[4,5-b]indole (5).

Effects of 2-indolecarbohydrazides on thromboxane synthetase activity and on in vitro and ex vivo blood platelet aggregation. New selective inhibitors.

Platelet antiaggregatory action of 42 synthetic 2-indolecarbohydrazides was studied observing their actions on arachidonic acid (AA) and adenosine-5-diphosphate (ADP) induced platelet aggregation. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on those compounds whose previous activities included inhibition of AA induced platelet aggregation and inhibition of the second wave of aggregation using ADP as the aggregating agent. Those compounds which demonstrated inhibition of TXB2 with increased PGE2 were subsequently tested with PGH2 as the aggregating agent.

Selectivity of an indole-hydrazide derivative as inhibitor of mouse brain type A monoamine oxidase.

The first indole-hydrazide, 1-[2,-(3-methyl)-5-benzyloxyindolyl]carbonyl-2-isopropyl hydrazide (IH-3), that irreversibly inhibits mouse brain type A monoamine oxidase is measured by 5-hydroxytryptamine deamination. The concentration required in vitro to inhibit this isoenzyme is about 7 X 10(-8) mol/l. Other biochemical and pharmacological features of this potential antidepressant are presented.

Effects of antibiotics on platelet functions in human plasma in vitro and dog plasma in vivo.

The effects of 31 antibiotics on platelet aggregation in human plasma in the presence of adenosine 5'-diphosphate were studied. The marked activity of tetracycline hydrochloride led to a study of its effects on various platelet functions in vivo in dogs.

New 5-hydroxy-2-indolecarbohydrazides as platelet aggregation inhibitors in ethylene glycol.

The effect of ethylene glycol on blood platelet aggregation was examined using a previously described method. This method also was used to investigate several derivatives of 2-indolecarbohydrazide in vitro. All compounds inhibited platelet aggregation induced by collagen, epinephrine, or adenosine diphosphate at concentrations below 5 x 10(-4) M.

Synergistic activity of gentamicin plus carbenicillin upon Pseudomonas aeruginosa: its relationship with pyocin and antibiotic susceptibility.

The synergistic effect of combinations of gentamicin and carbenicillin, as well as the type or subtype of the pyocins produced, were investigated in 170 strains of Pseudomonas aeruginosa isolated from clinical specimens. A high proportion of strains were synergistically inhibited (73.5%), but among strains producing pyocins 7, 14 and 31, synergy was infrequent or absent.