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Biomedical subjects

P Ferrari

Publications and source records attributed to P Ferrari.

At least 397 records · Page 22Linked to original sources

Hypotensive action and side-effects of flutonidin in normal subjects. A double-blind controlled trial.

In a double blind study, planned as a 7 x 7 latin square, three oral doses of flutonidin (0.5, 1, 2 mg), of clonidine (0.0075, 0.150, 0.300 mg) and of a placebo were administered to 7 normal volunteers on 7 different treatment days, with an interval of 3 days. On each treatment day sitting blood pressure, heart rate and reaction time were measured, and sedation and dry mouth evaluated before the 1, 2, 3, 4, 6, and 8 h after administration. The placebo did not modify the basal value of any variable. Flutonidin and clonidine produced dose-related effects on blood pressure, heart rate, sedation and dry mouth, but did not influence reaction time. Analysis of the dose-response curves demonstrated that the effect of flutonidin was one-fifth to one-twelfth that of clonidine, depending on which variable was considered.

Adult↗

Metabolites of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino]pyridazine dihydrochloride in rat urine.

In 24 hr urine of rats orally given 150 mg/kg of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino]pyridazine dihydrochloride (DL 150), no unchanged compound was detected. Three metabolites, less polar than DL 150, were isolated, their structures assigned by UV, MS, IR and 1H NMR spectroscopies, and confirmed by synthesis. They are: 3-[bis-(2-hydroxyethyl)amino]-6-isopropoxypyridazine (1); 3-[bis-(2-hydroxyethyl)amino]pyridazine (2); 3-methyl-6-[bis-(2-hydroxyethyl)amino]-s-triazolo[4,3-b]pyridazine (3). The metabolism of DL 150 in the rat follows some of the metabolic pathways reported for hydralazine.

Animals↗

[Cardiovascular effect of 1,2,4-benzothiadiazine-1,1-dioxide derivatives. VIII].

A series of carboxy- and carbomethoxyalkyl derivatives of 3-amino-1,2,4-benzothiaidazin-1,1-dioxide either substituted or unsubstituted in the benzene ring [compounds (I leads to XVIII)] was prepared and tested for cardiovascular activity. It was found that the introduction of a carboxy-or carbalkoxy-group in the omega position of 3-alkylamino derivatives of 1,2,4-benzothiadiazine-1,1-dioxide usually causes marked decrease or abolition of the cardiovascular activity shown by the parent compounds. The negative effect on the pressor trace (hypotension and increase in differential pressure) is more frequent and significant than that on bradycardial activity.

Animals↗

[Heteroarylalkanoic acids with potential anti-inflammatory activity].

A series of (3-oxodihydro-1,2,4-benzothiadiazin-1,1-dioxide-3-yl)acetic acids [compounds of type (A)] and (1,2,4-benzothiadiazin-1,1-dioxide-3-yl)oxyacetic acids [compounds of type (B)] were synthesised and tested for antiinflammatory activity. Preliminary tests showed certain compounds to have a significant level of antiinflammatory activity in rat paw edema induced by carrageenan. It was found that the antiinflammatory activity of this series of compounds depends on the nature, number and position of the substituents on the benzene ring.

Acetates↗

Increase in plasma extracellular fluid volume ratio caused by bilateral nephrectomy in patients on maintenance hemodialysis.

Changes, observed in rats after bilateral nephrectomy, in blood pressure and in the relation betwen plasma volume-extracellular fluid volume or plasma volume-interstitial fluid volume, are consistent with the postulation that the kidney secretes a substance that regulates, to some degree, the compliance of the interstitial space. In order to evaluate the possibility that this also occurs in humans, we have carried out a retrospective analysis of measurements of extracellular fluid volume, plasma volume, and blood volume made prior to and after bilateral nephrectomy in a group of 9 patients. It was observed that significant increases had occurred in both the plasma-extracellular fluid volume ratio (0.22 before, 0.26 after) and in the blood-extracellular fluid volume ratio (0.27 before, 0.32 after). These data are consistent with a reduction in compliance of the interstitial compartment caused by bilateral nephrectomy in man, even though other explanations cannot be excluded.

Adult↗

Polymorphism of 1-methyl-2-nitro-5-vinylimidazole.

Three polymorphic forms of 1-methyl-2-nitro-5-vinylimidazole, a potential antimicrobial drug, have been isolated and characterized by thermomicroscopy, differential scanning calorimetry, infrared spectroscopy and X-ray powder diffraction. On the basis of some infrared bands, the hypothesis has been made that the different packing of forms I and II was due to the existence of the molecule in two different conformations in the two forms. The direct confirmation of the hypothesis has been sought by X-ray diffraction of single crystals, but a suitable crystal was obtained only for form II. Form II is orthorhombic, space group Pbca, with unit-cell dimensions: a = 13.05, b = 10.83, c = 10.21 A; Z = 8. From the X-ray analysis, carried out by direct methods, the molecule is planar and the vinyl group is cisoid to the heterocyclic CH group. Then, the existence of the molecule as transoid conformation in form I still remains a hypothesis.

Calorimetry, Differential Scanning↗

[Cardiovascular action of 1,2,4-benzothiadiazine-1,1-dioxide derivatives. VI].

A series of 3,4-dihydro derivatives of 6-chloro-, 7-chloro-, 5,7-dichloro-, 6,7-dichloro-, 5,7-dibromo-, 5-nitro-7-chloro-, 7-nitro-, 7-amino-1,2,4-benzothiadiazine-1,1-dioxide, various substituted on the heterocyclic carbon, was prepared and tested for cardiovascular activity. It was found that in this series of compounds cardiac activity predominates and is exclusively of the depressant type. Bradycardial activity seems to be affected both by the nature of the substituent on the heterocyclic carbon atom and by the substituents on the benzene ring. An alkyl chain of three carbon atoms, normal or alpha-ethylsubstituted, on C3 and the presence of a chlorine atom in positions 6 or 7 seem to be the most significant structural features for this activity. Some of the substances tested showed a pressor effect (hypotension and/or increase in differential pressure).

Animals↗

[Cardiovascular action of 1,2,4-benzothiadiazine-1,1-dioxide derivatives. VII].

A series of dimethylamino-, diethylamino-, pyrrolidyl- and morpholylalkyl derivatives of 3-amino-1,2,4-benzothiadiazine-1,1-dioxide (compounds I leads to XX) was prepared and tested for cardiovascular activity. It was found that substitution of the alkyl group with the above mentioned groups in 3-amino-1,2,4-benzothiadiazine-1,1-dioxide derivatives in most cases causes marked dissociation of hypotensive activity from bradycardial activity and also disappearance or great reduction in the effect on differential pressure. It was also found that hypotensive activity is particularly dependent on the nature of the basic chain in the two components: length of the carbon chain between the two nitrogens and nature of the basic grouping. For the first component a chain of three carbon atoms seems the most effective and for the second the diethylamino group seems the most favourable. In addition, substituents in the benzene ring influence hypotensive activity, often positively, and 6,7-dichlorosubstitution in some compounds also affects the increase of differential pressure.

Animals↗

Polymorphism of rifampicin.

The antibiotic rifampicin shows polymorphism. Two crystalline forms, an amorphous form and four solvates (S I and S II from water; S III from tetrahydrofuran; S IV from carbon tetachloride) have been isolated and characterized by thermal analysis, infrared and X-ray powder spectroscopy. The functional I.R. bands have been interpreted as indicative of some structural features involved in the polymorphism: the intramolecular H-bonds between C23--OH and O=C--O--C25, C4--OH and O=C11, and C1--OH and O=C15. The relative physical stabilities of the various forms are reported.

Crystallization↗

Polymorphism and H-bonding of 2-[1(2H)-oxo-2-phthalazinyl]methylbenzoic acid.

The three crystalline and one amorphous forms of the title compound, so far isolated, have been characterized by differential scanning calorimetry, thermomicroscopy, infrared spectroscopy and X-ray powder diffraction. From I was obtained by solidification of the melt at 200 degrees; form II by crystallization from water/ethanol 1/1; form III by grinding of II; the amorphous form by rapid cooling of the melt or by evaporation to dryness of a chloroform solution. From II melts of about 200 degrees and immediately crystallizes into form I, which melts at 210 degrees. Form III transforms into I at 165 degrees. The infrared spectra of form I is different from that of forms II and III, while each form has a different X-ray powder diffraction. From consideration of the infrared functional absorption bands, it can be derived that form I is a dimer with H-bonds between the carboxylic groups, forms II and III are monomers with intramolecular H-bond between the carboxylic group and the hydrazide carbonyl, displaying different crystal packings, and the amorphous form is a mixture of both monomers and dimers, the latters in greater amount.

Benzoates↗

[The road].

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Adolescent↗