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Biomedical subjects

A Nunziata

Publications and source records attributed to A Nunziata.

13 recordsLinked to original sources

Safety and toxicological profile of the new antitussive levodropropizine.

Levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), a new antitussive drug, was submitted to toxicological studies. Acute toxicity, both oral and intraperitoneal, in rats and mice and oral toxicity in guinea-pigs was low. Subchronic and chronic toxicity studies were performed in rats and dogs. For both species the maximum tolerated oral dosage was 24 mg/kg/d. Dose-related clinical signs were observed, consisting mainly in salivation in rats and sedation, peripheral vasodilatation and increased heart rate in dogs. Liver toxicity was found in both species at higher dosages. In rats, food intake and body weight gain were reduced. There were no effects on fertility, nor any teratogenic effects. Foetal and peri- and post-natal toxic effects were observed in rats only at 150 mg/kg/d. A set of mutagenicity tests yielded negative results. Therefore, levodropropizine is safe up to dosages 10 times greater than the one intended for clinical use and only slight adverse reactions were recorded at a dosage 30 times greater.

Abnormalities, Drug-Induced

Possible adrenal involvement in hydroxyurea toxicity defense mechanisms.

Changes in blood biochemistry, resembling adrenocortical hyperfunction, induced by oral administration with hydroxyurea (HYD) at a dosage of 800 mg/Kg/d for 5 days (K+ and total protein decrease, total cholesterol increase) are not modified or enhanced (total protein) by adrenalectomy. Adrenalectomy dramatically enhanced the decrease of WBC and neutrophils normally induced by HYD. Replacement therapy with corticosterone attenuated and/or delayed the above changes. Normally-functioning adrenocortical tissue may play a role in protection against HYD haematological toxicity in the rat and the drug-induced hypothalamus pituitary mediated adrenocortical activation seems to represent a mechanism capable of counteracting drug toxicity.

Adrenalectomy

Cadmium alters arterial baroreflex control of heart rate in the conscious rat.

In conscious rats, a single oral dose of cadmium (Cd) chloride (up to 150 mg/kg) does not alter mean arterial pressure, heart rate and pressor response to phenylephrine 3, 7, and 14 days after loading. However, 150 mg/kg of Cd reduce reflex bradycardia and increase centrally mediated vagal decrease in heart rate. Therefore, it is suggested that Cd could modify baroreflex control of heart rate through an impairment of the afferent component of the reflex.

Animals

Pharmacological properties of new neuroleptic compounds.

RMI 61 140, RMI 61 144 and RMI 61 280 are newly synthetized N-[8-R-dibenzo(b,f)oxepin-10-yl]-N'-methyl-piperazine-maleates which show interesting psychopharmacologic effects. This work contains the results of a study performed with these three compounds, in order to demonstrate their neuropsycholeptic activity in comparison with chloropromazine (CPZ) and chlordiazepoxide (CPD). The inhibition of motility observed in mice shows that the compounds reduce the normal spontaneous motility as well as the muscle tone. The central-depressant activity is evidenced by increased barbiturate-induced sleep and a remarkable eyelid ptosis can also be observed. Our compounds do not show any activity on electroshock just as do CPZ and CPD. As to the antipsychotic outline, our compounds show strong reduction of lethality due to amphetamine in grouped mice and a strong antiapomorphine activity. They show also an antiaggressive effect and an inhibitory activity on avoidance behaviour much stronger than CPZ. We have also found extrapyramidal effects, as catalepsy, common to many tranquillizers of the kind of the standards used by us. As for vegetative phenomena, the compounds show hypotensive dose related action ranging from moderate to strong, probably due to an a-receptor inhibition. Adrenolytic activity against lethal doses of adrenaline, antiserotonin and antihistaminic effects, as well as other actions (hypothermia, analgesia, etc.) confirm that RMI 61 140, RMI 61 144 and RMI 61 280 are endowed with pharmacologic properties similar and more potent than those of CPZ. Studies on the metabolism of brain catecholamines show that they are similar to CPZ, although with less effect on dopamine level.

Aggression

[Diffuse pulmonary microlithiasis (a clinical case)].

The authors present a clinical case pertinent to a patient suffering from persistent dry cough and dyspnea by effort. It is described the diagnostic course that enables to identify a diffuse pulmonary microlithiasis, of rare cheeking, whose pathogenetic hypotheses and differential problems are tackled.

Adult

[Experimental analysis of interference between alpha-adrenergic stimulants with anti-hypertensive activity and the narcotic activity of pentobarbital].

The interactions of 3 classical alpha-adrenergic antihypertensives of prevalently central type (St 155 or clonidine St 600; BR 750 or guanabenz) with the narcotic effects of pentobarbital have been investigated in the Mus musculus. Interferences between convulsant drugs and spontaneous and coordinatory motor activity were also analysed in comparative studies.

Adrenergic alpha-Agonists