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Biomedical subjects

J Roquebert

Publications and source records attributed to J Roquebert.

At least 37 records · Page 2Linked to original sources
PubMed1984

Effect of dihydroergocristine on blood pressure and activity at peripheral alpha-adrenoceptors in pithed rats.

The effect of dihydroergocristine on blood pressure and peripheral alpha-adrenoceptors was examined in pithed rats. The pressor response to dihydroergocristine was reduced competitively by yohimbine and non-competitively by nifedipine, but not by prazosin or methysergide. These results show that vasoconstriction due to dihydroergocristine is mediated by alpha 2-adrenoceptors. Dihydroergocristine decreased the tachycardia elicited by electrical stimulation of the cardioaccelerator sympathetic nerves, this effect being antagonized by yohimbine. The pressor response to electrical stimulation of the spinal sympathetic outflow and to (-)-phenylephrine was reduced by dihydroergocristine suggesting competitive antagonism. It can be concluded that in pithed rats dihydroergocristine acts at the periphery as a competitive alpha 1-adrenoceptor blocker and an alpha 2-adrenoceptor agonist.

Animals↗
PubMed1984

Effects of raubasine stereoisomers on pre- and postsynaptic alpha-adrenoceptors in the rat vas deferens.

The actions of raubasine, tetrahydroalstonine and akuammigine were studied on pre- and postsynaptic alpha-adrenoceptors of the rat vas deferens. These three drugs competitively antagonized the effect of noradrenaline on postsynaptic alpha-adrenoceptors, yielding pA2 values of 6.57, 4.56 and 4.68 respectively. The presynaptic alpha-adrenoceptor antagonist activity of the drugs was quantitatively determined by studying the effect of increasing concentrations on the clonidine dose-response curve in the electrically stimulated vas deferens. The inhibitory effect of clonidine could be competitively blocked by these three compounds and the pA2 values for raubasine, tetrahydroalstonine and akuammigine were 6.02, 7.71 and 5.64 respectively. These results indicate that: akuammigine is a very weak antagonist at pre- and postsynaptic sites; raubasine acts preferentially at postsynaptic sites; tetrahydroalstonine is a highly selective presynaptic alpha-adrenoceptor blocking agent. The ratio of the pre/postsynaptic potency declines in the order tetrahydroalstonine greater than akuammigine greater than raubasine.

Animals↗
PubMed1983

Alpha 1- and alpha 2-adrenoceptor selectivity of moxisylyte (thymoxamine) and its metabolites in the pithed rat.

The selectivity of moxisylyte and its two metabolites deacetylmoxisylyte and demethyldeacetylmoxisylyte, for alpha 1- and alpha 2-adrenoceptors has been investigated in the pithed rat. Alpha 2-adrenoceptor blockade was measured by antagonism of the inhibitory effect of clonidine on the tachycardia produced by electrical stimulation of the cardiac accelerator nerves and of the pressor response to B-HT 933. alpha 1-Adrenoceptor blockade was measured by inhibition of the pressor response to (-)phenylephrine and to stimulation of the sympathetic outflow from the spinal cord. The three drugs (5 X 10(-6) to 2 X 10(-5) mol/kg i.v.) did not affect the inhibitory effect of clonidine and were equipotent as antagonists of the pressor response to B-HT 933, but only at the higher dose (10(-5) mol/kg). Moxisylyte and its metabolites (2.5 X 10(-6) to 10(-5) mol/kg i.v.) reduced the pressor response to (-)phenylephrine and to stimulation of the sympathetic outflow of the spinal cord in a dose-dependent manner. They were much more effective against (-)phenylephrine than B-HT 933. These results indicate that the three drugs are preferential alpha 1-adrenoceptor antagonists in vivo.

Animals↗
PubMed1982

alpha-Adrenoceptor blocking properties of raubasine in pithed rats.

1 Raubasine was compared with yohimbine and corynanthine in pithed rats. Antagonist activity at alpha 1-adrenoceptors was evaluated on the pressor response to electrical stimulation of the spinal sympathetic outflow and to phenylephrine administration, both being reduced by raubasine in the dose range 1 to 4 mg/kg. Corynanthine was quantitatively similar, but yohimbine was not only less potent but also in doses of 0.125 to 0.5 mg/kg enhanced the effects of electrical stimulation. 2 Antagonist activity at alpha 2-adrenoceptors was determined against the inhibitory effects of clonidine on tachycardia induced by electrical stimulation of cardiac sympathetic nerves and against the pressor responses to B-HT-933 injection. Raubasine up to 4 mg/kg, like corynanthine, did not affect the pressor responses to B-HT-933 nor did it reduce the inhibitory effect of clonidine. By contrast yohimbine reduced the response to BHT-933 and antagonized clonidine as well as enhancing the tachycardia caused by electrical stimulation. 3 The results indicate that, in vivo, raubasine, like corynanthine, is a selective antagonist at alpha 1-adrenoceptors and that yohimbine is more potent in blocking alpha 2-than alpha 1-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1982

Effects of thymoxamine and its metabolites on clonidine-induced hypotension and bradycardia in rats.

Thymoxamine and deacetylthymoxamine antagonized the hypertensive response of pithed rats to noradrenaline and clonidine, probably by inhibiting vascular post-synaptic alpha-adrenoceptors. N-demethyl-deacetylthymoxamine was inactive. Clonidine-induced reduction of tachycardia caused by electrical stimulation of the cardiac sympathetic nerve in pithed rats was antagonized by phentolamine but not by prazosin, thymoxamine, deacetylthymoxamine or N-demetyldeacetylthymoxamine. This suggests that prazosin and thymoxamine and its derivatives predominantly blocked alpha 1-adrenoceptors. In pentobarbitone-anaesthetized normotensive rats, prazosin, thymoxamine and deacetylthymoxamine decreased the hypotensive effect of clonidine, but had no significant effect on clonidine-induced bradycardia. These substances antagonized clonidine-induced hypotension in rats by the probable mechanism of inhibiting central alpha 1-adrenoceptors whose characteristics are similar to peripheral receptors. These data suggest that clonidine produced a hypotensive action in pentobarbitone anaesthetized rats via alpha 1-adrenoceptors and produced bradycardia via alpha 2-adrenoceptors.

Anesthesia↗
PubMed1981

Calcium antagonism of the inhibitory effects of fentanyl on the contraction of the nictitating membrane in cats.

The contractile responses elicited from the nictitating membrane of cats by postganglionic sympathetic nerve stimulation were decreased by fentanyl (10-20 micrograms/kg injected in the lingual artery). The inhibitory effect of fentanyl was preferential on responses elicited bu low frequency stimulation. Fentanyl (10-25 micrograms/kg) did not change the contractile response to noradrenaline and tyramine. The inhibitory effect of fentanyl was antagonized by naloxone. Increases in plasma calcium concentration did not alter the contractile responses to sympathetic nerve stimulation but antagonized the inhibitory effect of fentanyl in a dose-dependent manner suggesting a possible competitive antagonism.

Animals↗
PubMed1981

Pre- and postsynaptic alpha-adrenoceptor blocking activity of raubasine in the rat vas deferens.

1 The actions of raubasine, yohimbine and corynanthine at pre- and postsynaptic alpha-adrenoceptors were studied in the rat vas deferens. 2 Low frequency electrical stimulation of the isolated vas deferens of the rat produced regular contractions that were inhibited by low concentrations of clonidine. This inhibition was presynaptic in origin and involved alpha-adrenoceptors. 3 Presynaptic alpha-adrenoceptor antagonist activity was assessed by studying the effect of increasing antagonist concentrations on cumulative clonidine dose-response curves on the stimulated vas deferens. 4 Postsynaptic alpha-adrenoceptor antagonist activity in the isolated vas deferens was assessed by comparing control cumulative noradrenaline dose-response curves in the absence and in the presence of increasing concentrations of antagonists. 5 The results indicate that raubasine and corynanthine preferentially block postsynaptic alpha-adrenoceptors. Yohimbine is more potent in blocking pre- than postsynaptic alpha-adrenoceptors. The ration of the pre/postsynaptic potency declines in the order yohimbine less than raubasine less than corynanthine.

Adrenergic beta-Antagonists↗
PubMed1981

Antinoradrenergic activity of thymoxamine and its metabolites in rats.

The alpha-adrenoceptor blocking activity of thymoxamine and its two metabolites deacetylthymoxamine and N-demethyldeacetylthymoxamine was determined on the norepinephrine-induced contraction of rat vas deferens and thoracic aorta and the blood pressure increase induced by intravenously administered norepinephrine in anesthetized normotensive and pithed rats. In isolated rat vas deferens, the three drugs act as competitive antagonists (thymoxamine pA2 = 6.75;l deacetylthymoxamine pA2 = 6.57; N-demethyldeacetylthymoxamine pA2 = 6.20). At the level of the thoracic aorta, the three drugs act as antagonists with a dual mode of action (thymoxamine pA2 = 6.55--pD2' = 4.70; deacetylthymoxamine pA2 = 6.53--pD2' = 4.70; N-demethyldeacetylthymoxamine pA2 = 5.61--pD2' = 4.63). In anesthetized normotensive or pithed rats, thymoxamine and deacetylthymoxamine produce an antagonism of the hypertensive response to norepinephrine. Thymoxamine and deacetylthymoxamine present nearly the same alpha-blocking activity in vitro and in vivo. N-demethyldeacetylthymoxamine is less active.

Adrenergic alpha-Antagonists↗
PubMed1980

Metabolism of thymoxamine: identification of metabolites in rat.

Thymoxamine hydrochloride administered by mouth to rats at 25 or 100 mg kg-1 was excreted in the urine as the deacetyl and N-demethyl-deacetyl metabolites. These were completely sulpho- and glucuronoconjugated at 25 mg kg-1 but only partially so at the higher dose. Thymoxamine deacetylation in vitro is catalysed by plasma and hepatic cytosol esterases and the deacetyl metabolite undergoes N-demethylation catalysed by the cytochrome P 450 hepatic microsome mixed function monooxygenase system. Because of the rapidity of the deacetylation it is concluded that thymoxamine is a prodrug leading in vivo to the active deacetyl thymoxamine.

Animals↗
PubMed1980

In vitro and in vivo alpha-blocking activity of thymoxamine and its two metabolites.

The alpha-adrenoceptor potency of thymoxamine and its two metabolites deacetylthymoxamine and demethyldeacetylthymoxamine were determined on the contraction of rat vas deferens induced by noradrenaline, the blood pressure increase induced by noradrenaline given i.v. to dogs and the contraction of the nictitating membrane induced by electrical stimulation in cats. In vivo the three drugs were administered at 6.35 x 10(-6) mol kg-1 intravenously. Deacetylthymoxamine presented nearly the same alpha-blocking activity as the parent drug. This was ascribed in vivo to the rapid deacetylation of thymoxamine. Demethyldeacetylthymoxamine was less active. In vitro its pA2 was 6.20 +/- 0.09 compared with 6.75 +/- 0.20 for thymoxamine and 6.57 +/- 0.13 for deacetylthymoxamine. In vivo, it was inactive in dog and less active than the other two drugs soon after its administration in the cat. The oral LD 50 values in the mouse for the three drugs were respectively 0.81, 0.71 and 1.14 mmol kg-1 for thymoxamine, deacetylthymoxamine and demethyldeacetylthymoxamine.

Adrenergic alpha-Antagonists↗