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Biomedical subjects

P Demichel

Publications and source records attributed to P Demichel.

At least 19 recordsLinked to original sources
PubMed1992

Effects of quinpirole on autonomic nervous control of heart rate in rats.

The effects of quinpirole, a specific dopamine DA2 receptor agonist, on autonomic nervous control of heart rate, were studied in normotensive pithed rats, by analysing its action on the tachycardia and bradycardia evoked by electrical stimulation of the cardioaccelerator (10 V; 1 ms; 0.5, 1, 3, 6 Hz) and vagus (10 V; 1 ms; 3, 6, 9 Hz) nerves respectively. Quinpirole (10-50-100 micrograms kg-1 iv) reduced the cardioacceleration elicited by electrical stimulation but not that by noradrenaline (3 micrograms kg-1 iv). The effect on electrical stimulation was blocked by domperidone (0.5 mg kg-1 iv) but not by SCH 23390 (0.2 mg kg-1 iv) or idazoxan (0.3 mg kg-1 iv). At 1, 5, 10, 30 micrograms kg-1 iv, quinpirole decreased vagal but not acetylcholine-induced bradycardia. The effect on electrical stimulation was inhibited by domperidone (0.5 mg kg-1 iv) but not by SCH 23390 (0.2 mg kg-1 iv), prazosin (0.1 mg kg-1 iv) or idazoxan (0.3 mg kg-1 iv). The data point to the presence of presynaptic and/or ganglionic dopamine receptors in the sympathetic and parasympathetic innervation of the rat heart, where stimulation inhibits the release of neuromediators.

Animals↗
PubMed1992

Effect of quinpirole on neurogenic vasoconstriction in the in situ autoperfused hindquarters and renal vascular beds of the rat.

1. The effects of local administration of quinpirole were studied in the in situ autoperfused hindquarters and renal vascular beds, in order to assess whether presynaptic dopamine receptors in these vascular systems could play a role in the hypotensive effect of this agonist. 2. In both preparations, local injection of quinpirole did not alter perfusion pressure, but reduced the pressor response to electrical stimulation of the sympathetic innervation. Increases in perfusion induced by local administration of noradrenaline were not altered by quinpirole. 3. The inhibitory effect of quinpirole on the stimulation-evoked pressor responses was completely antagonized by intravenous administration of the DA2-receptor antagonist domperidone (0.5 mg kg-1) but not by the DA1-receptor antagonist SCH 23390 (0.3 mg kg-1) or the alpha 2-adrenoceptor antagonist idazoxan (0.3 mg kg-1). 4. The results indicate that quinpirole inhibits neurally induced pressor responses in the autoperfused hindquarters and renal vascular beds of the rat by stimulation of presynaptic dopamine receptors. These receptors may be involved in the hypotensive action of quinpirole in the rat.

Adrenergic alpha-Antagonists↗
PubMed1991

Pharmacological characterization of dopamine receptors in parasympathetic innervation of rat heart.

The action of dopamine agonists (apomorphine, bromocriptine, pergolide and quinpirole) on the bradycardia induced in vivo by electrical stimulation of the vagus nerves was studied in pithed rats pretreated with atenolol. The dopamine agonists decreased significantly the vagal-induced but not the acetylcholine-induced bradycardia. The first effect was blocked by (S)-sulpiride or domperidone but not by yohimbine, prazosin or SCH 23390. Both effects were antagonized by methylatropine. The data suggest the presence of presynaptic and/or ganglionic dopamine DA2 receptors in the parasympathetic innervation of the rat heart, stimulation of which inhibits the release of acetylcholine.

Acetylcholine↗
PubMed1987

Agonist/antagonist activity of ergocristine at alpha-adrenoceptors in the rat.

(1) The action of ergocristine at alpha-adrenoceptors was studied in vivo in the pithed rat, and in vitro on the rat isolated vas deferens. (2) In the pithed rat, the pressor response to ergocristine was reduced competitively by yohimbine, but not by prazosin. (3) Ergocristine decreased the tachycardia elicited by electrical stimulation of the cardioaccelerator sympathetic nerves, this effect being antagonized by yohimbine. (4) At postsynaptic alpha 1-adrenoceptors, on the vas deferens of the rat, ergocristine antagonized the contraction induced by phenylephrine in a competitive manner (pA2 = 7.85). (5) These results show that vasoconstriction due to ergocristine is mediated by alpha 2-adrenoceptors and that, in the rat, ergocristine acts as an alpha 2-adrenoceptors agonist, and an alpha 1-adrenoceptors antagonist.

Animals↗
PubMed1985

Alpha-adrenergic agonist and antagonist activity of dihydroergotoxine in rats.

The alpha-adrenergic activity of dihydroergotoxine had been studied in both pithed and urethane or pentobarbitone anaesthetized rats. In anaesthetized rats, blood pressure effects varied with the anaesthetic agent: hypotension with urethane, hypertension with pentobarbitone. This latter pressor response was a peripheral effect. In pithed rats, the vasopressor response to dihydroergotoxine was reduced competitively by yohimbine, and non-competitively by nifedipine, but not by prazosin or methysergide, showing that the vasoconstriction is mediated by alpha 2-adrenoceptors. Dihydroergotoxine decreases the tachycardia elicited by stimulation of the cardioaccelerator nerves, this effect being antagonized by yohimbine. It also reduced the pressor response to (-)-phenylephrine. These results indicated that, on the peripheral vascular system of the rat, dihydroergotoxine acts as an alpha 1-adrenoceptor blocker and an alpha 2-adrenoceptor agonist.

Adrenergic alpha-Agonists↗
PubMed1984

Inhibition of the alpha 1 and alpha 2-adrenoceptor-mediated pressor response in pithed rats by raubasine, tetrahydroalstonine and akuammigine.

The relative potencies of raubasine, tetrahydroalstonine (THA) and akuammigine on alpha 1- and alpha 2-adrenoceptors were assessed by comparing their effects on the rise in blood pressure induced by stimulation of the sympathetic outflow from the spinal cord or by injection of noradrenaline in pithed rats. Akuammigine was inactive in both cases. Raubasine preferentially antagonized the effects of electrical stimulation while THA antagonized the effects of injected noradrenaline. The results suggest that raubasine preferentially blocks alpha 1-adrenoceptors while THA is more selective for alpha 2-adrenoceptors.

Animals↗
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↗
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↗
PubMedDate not supplied

NPFF, a FMRF-NH2-like peptide, blocks opiate effects on ileum contractions.

We studied the ability of NPFF, a FMRFamide-like peptide with certain antiopiate properties, to affect the inhibitory effect of morphine on the electrically induced contraction of guinea pig ileum. Neuropeptide FF had no effect when administered alone but reduced morphine inhibition in a noncompetitive manner. Neuropeptide FF also altered the inhibitory effect of opioid peptides as released by an intense electrical stimulation at 10 Hz. These results suggest that NPFF receptors exist in guinea pig ileum in association with opiate receptors, and that endogenous NPFF may play a role in the diarrhea observed in the morphine withdrawal syndrome.

Animals↗