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Biomedical subjects

N Decker

Publications and source records attributed to N Decker.

44 records · Page 3Linked to original sources
PubMed1982

Synthesis and cardiovascular activity of a new series of cyclohexylaralkylamine derivatives related to perhexiline.

A series of 24 cyclohexylaralkylamine derivatives related to perhexiline has been synthesized and screened for cardiovascular activity. All the compounds contained an exocyclic amine which was substituted either by an alkyl, cycloalkyl, or aralkyl group. In the hope of further reducing toxicity, the synthesis of p-tolyl- and p-hydroxyphenyl derivatives 23 and 24 was undertaken. The effect of separating the cyclohexylamine moiety with respect to the aromatic nucleus has been systematically examined. The pharmacological investigations were directed to a search for compounds having an activity better than perhexiline according to the following order of criteria: (1) alpha-adrenolytic activity; (2) increase of coronary blood flow; (3) calcium antagonism. Several compounds were more potent and exhibited lower toxicity than perhexiline. Further detailed pharmacological investigations (tension time index and decreased cardiac work) have led to the selection of N,2-dicyclohexyl-2-phenethylamine (3) for clinical trials, which are now under way.

Adrenergic alpha-Antagonists↗
PubMed1982

Effects of N-aralkyl substitution of beta-agonists on alpha- and beta-adrenoceptor subtypes: pharmacological studies and binding assays.

The pharmacological and binding properties of four beta-adrenomimetic drugs with N-alkyl substitutions (isoprenaline, terbutaline, salbutamol and soterenol) were compared with those of four corresponding drugs with N-aralkyl substitutions (protokylol, ME 506, salmefamol and zinterol). BD-40 A, a very powerful beta 2-agonist with a related chemical structure, was also included in this study. The beta 1- and beta 2-activities of these drugs were determined on guinea-pig atria and trachea, their alpha-adrenolytic activity was measured on rat aorta and their affinities (Ki) for alpha 1- and alpha 2-adrenoceptors on rat cortical membranes were assessed using [3H]prazosin and [3H]yohimbine. In this group of beta-agonists, substitution of the N-alkyl by an N-aralkyl group had a variable effect on the beta 2-selectivity whereas alpha-adrenolytic properties were always enhanced. An increase of the affinities (Ki) for both alpha 1- and alpha 2-adrenoceptors was found but the effect was much more pronounced for alpha 1-adrenoceptors. These results indicated that the alpha-adrenolytic activity observed with the N-aralkyl beta-agonists was selective for alpha 1-adrenoceptors.

Adrenergic beta-Agonists↗
PubMedDate not supplied

[Iatrogenic medication: estimation of its prevalence in French public hospitals. Regional Centers of Pharmacovigilance].

The French network of Regional Centres of Pharmacovigilance has made an estimation of the occurrence of adverse drug reactions in a representative sample of patients in French public hospitals (departments of medicine, of surgery and of geriatrics). The study looked at one specific day in the spring of 1997. Each observed case of adverse drug reaction was validated. The total sample comprised 2132 patients of whom 969 were in a university hospital and 1163 in a general hospital. The hospitals and units concerned are representative of the country as a whole. One adverse drug reaction at least was present for 221 patients on the day of the investigation. This means a prevalence rate of 10.3 per cent (95 per cent CI: 8.7 to 11.9 per cent). In 33 per cent of cases (95 per cent CI: 26 to 42 per cent), the observed effects were rated as serious. From an incidence rate of 1.8 per cent (95 per cent CI: 1.0 to 25 per cent) on one specified day it can be estimated that in France an adverse drug reaction will occur in about 1,300,000 patients per year during a stay in hospital.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

Coronary vasodilation and positive inotropic effect of non steroidal cardiotonics.

The effects of several cardiotonic agents (ARL-115, Amrinone, RMI 82-249, Milrinone, CI-914, RO 13-6438 and APP 201-533) were compared with those of ouabain on pig isolated coronary artery, guinea-pig isolated atria and guinea-pig perfused heart to compare vasodilatory and inotropic responses. Like ouabain, all compounds tested produce positive inotropic and chronotropic effects in isolated atria and on perfused heart, and induce relaxation in precontracted pig coronary artery and coronary vasodilation on perfused heart, except ouabain which induces vasoconstriction. The results indicate that non steroidal cardiotonics exert positive inotropic and coronary vasodilatory effects.

Animals↗
PubMedDate not supplied

[Cardiovascular effects of urapidil].

The cardiovascular effects of urapidil have been investigated in the anesthetized rat. The mechanism of the hypotensive action of this drug has been tested in vitro on the isolated rat aorta and in vivo by intracerebroventricular injections. The peripheral vasoconstrictor effect has been studied in the pithed rat. In the pithed rat, the thoracic part of the spinal cord was electrically stimulated in order to induce a tachycardia. The reduction of this tachycardia by a drug is due to its inhibitory effect on cardiac sympathetic nerves endings. Intravenous urapidil produces a significant hypotension without change in heart rate. Directly injected into the brain cavities, urapidil produces a hypotensive effect only at very high doses (1 mg/kg). This hypotensive action of urapidil appears therefore to be mainly of peripheral origin. Urapidil antagonizes competitively the contraction of the aorta induced by norepinephrine. The drug has alpha-blocking properties which explain its hypotensive action. On the other hand, urapidil provokes a weak vasoconstrictor effect in the pithed rat and induces a presynaptic inhibition in the heart which may explain the lack of heart rate change during the hypotensive effect of the drug. Urapidil may therefore also stimulate post or presynaptic alpha 2-adrenoceptors.

Animals↗