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Biomedical subjects

G Miragoli

Publications and source records attributed to G Miragoli.

At least 19 recordsLinked to original sources
PubMed1996

Investigation of the positive inotropic action of 6,7-dimethoxy-3-cyano-3,4-dihydrocarbostyril.

6.7-Dimethoxy-3-cyano-3.4-dihydrocarbostyril (7A61, 1), a 2-quinolinone derivative, showed interesting cardiotonic properties in vitro. It exerted potent positive inotropic effects, without any change in heart rate, in guinea pig atrial preparations, and its effects were not dependent upon inhibition of phosphodiesterases, opening of Na+ channels, or inhibition of adenosine receptors. Notwithstanding its structural relationships with milrinone, vesnarinone, and other quinolinones endowed with cardiotonic activity, it appeared that 7A61 does not share any of the main mechanisms of action involved in the pharmacological activity of these compounds. Other experiments also excluded the involvement of other well known mechanisms of cardiac stimulation, such as adrenergic receptor activation or opening of Ca++ channels, the mode of action of 7A61 remaining unexplained. However, contrary to milrinone, 7A61 did not exert cardiotonic effects in human ventricular muscle preparations, thus discouraging further investigation. Although the lack of effect on human heart could not be predicted from the results obtained in several cardiac preparations commonly used in laboratory investigations, the scarce efficacy of 7A61 in comparison with milrinone in dog and cat papillary muscle and in guinea pig ventricular muscle suggests the utility of the latter preparations in laboratory experiments aimed at selecting new potential cardiotonic agents.

Animals↗
PubMed1989

Cardiovascular and renal action of dopaminergic prodrugs.

The possibility of exploiting the cardiovascular and renal action of dopamine for therapeutic purposes is enhanced by its conversion into orally active prodrugs. Following an outline of the medicinal chemistry bases of the development of these prodrugs, laboratory and clinical pharmacology of ibopamine, levodopa, gludopa, and TA-870 are reviewed, pointing out the interesting indications of various preliminary studies in heart failure, essential hypertension, and renal failure on the one hand, and the extensive therapeutic experience with ibopamine as an "inodilator" in the chronic treatment of congestive heart failure on the other hand. New experimental results are also reported for ibopamine and for the novel prodrug Sim 2055, i.e., epinine-4-O-phosphate. The latter is shown to act as a selective renal vasodilator on oral administration in dogs and it is therefore proposed for clinical investigation in renal failure and in essential hypertension.

Animals↗
PubMed1987

Pharmacological characterization of epinine 3-O-sulphate and 4-O-sulphate.

Ibopamine, the diisobutyric ester of N-methyldopamine, is able to increase cardiac output and induce vasodilatation on oral administration. While the pharmacodynamic activity of ibopamine is rather long-lasting, N-methyldopamine, i.e. ibopamine's primary metabolite, can be detected in plasma only for a short time after the administration. We have investigated the pharmacological activity of N-methyldopamine 3-O-sulphate and 4-O-sulphate, since the plasma levels of these conjugated metabolites are higher and last longer than those of N-methyldopamine. These compounds appeared to be devoid of any pharmacodynamic activity both in vivo on the main hemodynamic parameters in dog and on diuresis in rat, and in vitro on cat papillary muscle and rabbit ear artery. Consequently, the duration of ibopamine hemodynamic effects cannot be related to these circulating metabolites, thus other hypotheses should be taken into consideration.

Animals↗
PubMed1986

Effect of ibopamine on diuresis and arterial blood pressure in anesthetized rats and its interactions with dopaminergic and alpha- and beta-adrenergic antagonists.

The present paper reports a study of the effect of ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine (epinine), on diuresis and blood pressure in anesthetized rats. The results obtained demonstrate that ibopamine, administered orally at doses of 12.5 to 200 mg/kg, caused a dose-dependent diuresis. The increase in blood pressure was moderate and of short duration. The diuretic effect of ibopamine was antagonized by d-sulpiride, haloperidol, bulbocapnine and phenoxybenzamine, but not by l-sulpiride and l-propranolol. The increase in blood pressure was antagonized by phenoxybenzamine only. The diuretic effect of ibopamine in rats reflects agonist activity at dopamine receptors and, in part, alpha-adrenoceptors and is independent of beta-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1986

Activity of ibopamine on some isolated organs.

The pharmacological activity of ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, was compared with that of epinine (N-methyldopamine) and dopamine on some isolated organs. The results of this study show that ibopamine and epinine exerts a positive inotropic effect on cat papillary muscle by stimulating the cardiac beta 1- and alpha-adrenoceptors; a positive chronotropic effect on cat right atrium by stimulating the cardiac beta 1-adrenoceptors; a relaxing effect on guinea-pig trachea by stimulating beta 2-adrenoceptors; a relaxing effect on rabbit splenic artery pretreated with phenoxybenzamine and contracted with PGF2 alpha by stimulating the DA1 receptors; an inhibitory effect on the vasoconstriction of rabbit ear artery induced by electrical stimuli by stimulating the DA2 receptors. Esterase activation, either by organ or plasma enzymes, appeared to be a prerequisite of ibopamine activity. Suppression of this activity by esterase inhibitors confirmed that the pharmacological responses are related to the formation of epinine. The magnitude and rate of response of some isolated organs to ibopamine appeared to be related to the esterase content of the tissue.

Animals↗
PubMed1986

Effect of ibopamine on diuresis in conscious rats in normal and experimentally altered conditions.

Diuretic effect of orally administered ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, was studied in normally hydrated and in experimentally oliguric rats. In normal rats ibopamine proved to be active in increasing urine volume as well as sodium and chlorine excretion. The diuretic effect set in rapidly and reached the maximum in the first 2 h after treatment; repeated daily treatment constantly increased urine and ions excretion. Ibopamine proved to be more active in oliguric than in normal rats; when administered orally in combination with furosemide it maintained its diuretic effect, which was additional to that of furosemide. Possible ibopamine interaction with antidiuretic hormone and sodium reabsorption as well as its use also in combination with diuretic agents in renal failure are discussed.

Animals↗
PubMed1986

Activity of ibopamine on central nervous system in mice and rats.

Ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine has proved to be able to induce cardiovascular and renal effects after oral administration which were comparable to those of dopamine injected intravenously. In the present paper ibopamine was investigated on some behavioural, motility and biochemical tests with a view to assaying its possible activity on the central nervous system (CNS). The results obtained show that ibopamine has no significant activity on CNS.

Adenylyl Cyclase Inhibitors↗
PubMed1979

[Cryoglobulinemia syndrome and liver diseases. Case reports].

Six cases of an association of liver disease with a cryoglobulinaemia syndrome are described. An account of their clinical, body fluid and anatomopathological pictures is followed by a discussion of their possible causes in the light of the relevant literature. It is felt that no assessment can be made of the primary nature of either disease in associations of this kind. In addition to cases in which prior liver disease or exposure to hepatitis virus can be shown, in fact, there are other situations in which liver disease was present before the manifestation of cryoglobulinaemia. Repeated antigen stimulus triggers the antibody response leading to the formation of cryoprecipitating complexes. In most cases, the nature of such antigen is not known, since HB virus or any other virus, bacterial product, or cell catabolism product either eliminated in insufficient quantities, or produced in abnormal quantities, may be responsible.

Adult↗
PubMed1979

Protective effect of creatinol O-phosphate (COP) on ventricular fibrillation and death induced by intravenous CaCl2 in mice.

The activity of N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate, COP) on the acute toxicity of CaCl2 in mice was studied. The results obtained in the present investigation show that COP administered i.v. is able to antagonize, in a dose-dependent way, the lethal ventricular fibrillation provoked by CaCl2 in unanesthetized mice. Prenalamine and cinnarizine, two calcium antagonistic compounds, proved to be active in a way qualitatively similar to COP.

Animals↗
PubMed1979

Protective effect of creatinol O-phosphate (COP) on some experimental arrhythmias in vitro and in vivo.

The activity of N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate, COP) on two in vitro and in vivo experimental arrhythmias was investigated. The substance proved to be active in delaying the onset time of aconitine induced arrhythmias in guinea-pig atria. COP showed also a definite antagonizing activity against chloroform-induced ventricular fibrillation in mice.

Aconitine↗