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M C Breschi

Publications and source records attributed to M C Breschi.

At least 55 records · Page 3Linked to original sources
PubMed1988

An anomalous effect of N-isopropyl substitution in determining beta-adrenergic activity.

We report unexpected results in an investigation of cyclic analogues of dopamine and norepinephrine possessing the structures 1-(aminomethyl)-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene (3) and 1-(aminomethyl)-5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthalenol (7). N-Isopropyl substitution of these compounds, providing 4 and 8, brings about the total disappearance of their stimulant activity on beta-adrenergic receptors. On the basis of current knowledge about the structure-activity relationship of adrenergic drugs, it is difficult to provide an explanation for these results; however a tentative rationalization based on conformational considerations is suggested.

1-Propanol↗
PubMed1987

Postsynaptic effects of alpha agonists on adrenoceptors of the reserpinized rat vas deferens.

The activities of the alpha-1 antagonist prazosin and alpha-2 antagonist yohimbine were evaluated against noradrenaline (NA), methoxamine (Me) and clonidine (Clo) on the reserpinized rat vas deferens. Prazosin antagonized competitively Me but not NA and Clo. On the other hand yohimbine showed a low and not competitive antagonism towards all the three agonists. Similar results were obtained when the antagonistic activities were tested in the presence of the alternative antagonist, in the attempt to isolate a single receptor population. We can conclude that the smooth musculature of the rat vas deferens contains prevalently alpha-1 adrenoceptors and a small population of NA activated receptors resistant to alpha-2 antagonists.

Adrenergic alpha-Agonists↗
PubMed1987

Role of the (acyloxy)methyl moiety in eliciting the adrenergic beta-blocking activity of 3-(acyloxy)propanolamines.

Some totally aliphatic 3-(acyloxy)propanolamines were synthesized with the aim of testing whether beta-blocking activity could be obtained from this class of drugs, even in the absence of an aromatic group. The significant and, in most cases, competitive beta-blocking activity shown by the compounds under examination, together with the results of a theoretical study in which their reactivity was compared with that of other adrenergic beta-blocking drugs, seems to confirm a hypothesis previously advanced on the basis of knowledge about the action mechanism of adrenergic beta-blocking drugs and of the results of structural studies. It was also possible to suggest some considerations about the role played by the (acyloxy)methyl portion of 3-(acyloxy)propanolamines in eliciting their adrenergic beta-blocking activity.

Adrenergic beta-Agonists↗
PubMed1986

Conformational effects on the activity of drugs. 11. Stereostructural models for the direct activation of the alpha- and beta-adrenergic receptor.

Two kinds of cyclic analogues of norepinephrine (NE, 7) and isoprenaline (ISO, 8), in which the C(1)-C(2) side chain of these amino alcohols is incorporated in its preferred conformation in the ring of the 2-(3,4-dihydroxyphenyl)-morpholines 9 and 10 (2-DPMs) and in the ring of the 3-(3,4-dihydroxyphenyl)-3-piperidinols 11 and 12 (3-DPPs), respectively, were synthesized and assayed for their adrenergic activity on various isolated preparations. The 2-DPMs and the 3-DPPs showed an alpha- and beta-agonist activity comparable to that of NE and ISO and to that of the trans-2-amino-5,6-dihydroxytetrahydronaphthalen-1-ols 13 and 14 (2-ADTNs), which represent another kind of semirigid analogue of NE and ISO. Through a comparison of the stereo structures of the compounds examined and of their pharmacological properties, it was possible to suggest a spatial situation in which the pharmacophoric groups of the adrenergic drugs examined (aryl moiety, amine nitrogen, and alcoholic or ethereal benzylic oxygen) should interact at the receptor site. This spatial situation corresponds to the one found in the preferred conformation of NE and ISO. It was also possible to construct two theoretical three-dimensional molecular models that provide information about steric requirements for the direct activation of alpha- and beta-adrenoceptors, respectively.

Animals↗
PubMed1985

An interdisciplinary approach to the design of new structures active at the beta-adrenergic receptor. Aliphatic oxime ether derivatives.

On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenoceptors; the beta 2/beta 1 selectivity ratio indicated that they are more active on the tracheal than on the cardiac beta-receptor. The chemical reactivity of the AOEDs was studied through the calculation of the electrostatic molecular potential (EMP) on a model compound in its preferred conformation. The results showed that the EMP trend agrees with that previously calculated for other beta-blocking drugs.

Adrenergic beta-Antagonists↗
PubMed1985

Fluorescence in sections of cardiac muscle from rats acutely treated with 4'-0-tetrahydropyranil-adriamycin hydrochloride (THP).

An investigation was undertaken of the capacity of thepirubicin (THP), a new anthracycline derivative with reduced cardiotoxicity, to be fixed in the myocardial fibre, as compared with that of adriamycin hydrochloride (ADR), using a method based on the histofluorescence of tissues treated in vivo with anthracyclines. Histological examination of heart sections from rats perfused with either THP or ADR showed similar results. The major difference was the lower quantitative localization of THP in the cytoplasm, although this quantitative difference was not so pronounced in the nuclei. This suggests that cardiac lesions may be due not to the basic action of anthracyclines on DNA but to collateral effects not yet identified.

Animals↗
PubMed1983

Conformational effects on the activity of drugs. 10. Synthesis, conformation, and pharmacological properties of 1-(2,5-dimethoxyphenyl)-2-aminoethanols and their morpholine analogues.

In order to obtain a better understanding of the effects that structural parameters have on the changes of adrenergic activity when 1-aryl-2-aminoethanol derivatives are converted into their corresponding 2-arylmorpholine cyclic analogues, we synthesized 1-(2,5-dimethoxyphenyl)-2-aminoethanol derivatives 5-7 and their morpholine analogues 8-10. The preferred conformation of amino alcohols and their cyclic analogues have been determined through an H NMR and IR study. Compounds 5 and 6 showed both alpha-stimulating and alpha-blocking activity on rat vas deferens, the effect depending on the concentration employed; on the same isolated tissue, N-isopropyl derivative 7 and the morpholine analogues 8-10 exhibited only alpha-blocking activity. As for the beta-adrenergic activity, only the open-chain compound 7 possessed a moderate blocking effect on isolated guinea pig atria. The results of this work seem to indicate that the changes of pharmacological activity involved in the transformation of the adrenergic drugs into their morpholine analogues are influenced more by characteristic features of the aromatic moiety than by the ethanolamine or propanolamine structure of the drugs.

Animals↗
PubMed1983

A modification of the soxhlet apparatus for drug extraction from biological fluids.

The authors suggest a method to isolate drugs and toxic substances from biological fluids which appears to be of easier and better applicability than other systems, because it allows the extraction by means of a hot solvent, reduces manual operations and the waste of solvent, and shortens the time of execution for the researchers. A mathematical formula is proposed in order to evaluate the recovery-time curves of any drug shortly and with better accuracy.

Amitriptyline↗
PubMed1982

Simultaneous histochemical demonstration of noradrenergic nerves and tissue components in guinea-pig renal pelvis after treatment with daunomycin.

A standard histochemical technique for detecting catecholamines has been applied to tissues from the renal pelvis of untreated and daunomycin-pretreated guinea-pigs. Under the fluorescence microscope, muscular, mucosal, and endothelial cells exhibited the drug-specific orange-red fluorescence, in contrast to the dark background of control tissues. The presence of daunomycin in the cells also greatly improved the visibility of numerous noradrenergic fibres which appeared to originate from perivascular plexuses and distribute to the smooth cells. A dense noradrenergic innervation was detected in the submucosa, but the epithelium did not contain any yellow-green fluorescent fibres. A typical arrangement was observed consisting of muscular, nervous and vascular components, enveloped by connective tissue: this formation appeared to be related to the system modulating the pacemaker activity of the renal pelvis.

Animals↗
PubMed1980

Noradrenergic innervation of the heart in untreated and daunomycin-pretreated animals.

The innervation of guinea-pig and rat cardiac tissue consists of thin noradrenergic axons running parallel to the myocardial fibres and producing well-developed fluorescent networks which are denser in guinea-pig tissue. Transverse sections of arterial vessels exhibit a marked polar-like disposition of adrenergic nerves, which mainly appear to be concentrated in two opposite areas. Tissue sections from daunomycin-treated animals fluoresced a striking orange-red. This drug-specific fluorescence emanated from all parts of the ventricular tissue, with particular intensity in the nuclei. Neither the density nor the shape of the adrenergic nerves were affected by treatment with the drug. Despite penetration and storage of the antibiotic into the ventricular tissue, cardiotoxicity was not found in the present study.

Adrenergic Fibers↗
PubMed1977

Histochemical studies of noradrenergic innervation of the liver in untreated and daunomycin-pretreated guinea-pigs.

The pattern of noradrenergic innervation of guinea-pig hepatic tissue was examined by using the fluorescence method of Falk et al. (1962). The distribution of monoaminergic nerve fibers in untreated animals was clearly evident at the level of the portal vein, the hepatic artery and the bile duct. The hepatic artery was the most densely innervated. Mast cells and Kupffer cells had no connection with the adrenergic fibres. In daunomycin-pretreated animals, the hepatic cells appeared to be deep red in colour owing to the presence of the antibiotic. Some noradrenergic nervous fibres, never previously described, were unexpectedly distinguishable in the liver parenchyma against the background red colour of daunomycin-pretreated tissue. They appeared to be contiguous to the hepatocytes and were of different shapes: comma-like, V-like, or like a string of pearls. The nature and the functional role of these elements is briefly discussed.

Adrenergic Fibers↗
PubMed1977

Distribution and fate of alpha-naphthl-isothiocyanate (ANIT) in the organs and body fluids of the rat.

alpha-Naphthyl-isothiocyanate (ANIT) is a well known toxic substance which induces characteristic hepatic lesions. Its distribution in some organs and body fluids was investigated by using spectrophotometry, gas-chromatography and thin-layer chromatography. The results indicate that ANIT concentrates in the liver, kidneys and blood but not in the brain, urine and bile. Another five ANIT-like substances have also been examined, but no trace of them has been found in these organs and body fluids. The authors suppose that ANIT is metabolized to an unknown metabolite which is responsible for the toxic action of ANIT. None of the ANIT-like substances examined by us can be indentified with this metabolite.

1-Naphthylisothiocyanate↗