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Biomedical subjects

J Roquebert

Publications and source records attributed to J Roquebert.

At least 19 recordsLinked to original sources
PubMed1998

[Acute and chronic toxicity of saponins from Argania spinosa].

We evaluated the acute and chronic experimental toxicity of a water extract of saponins from Argania spinosa following oral and intraperitoneal (i.p.) administration in mice (Iops Ofa) and rats (Wistar). The DL50 obtained were 79 mg/kg for the i.p. route and 1,300 mg/kg for the oral route. For the chronic toxicity studies, we administred 100 and 200 mg/kg orally once a day during a 3 month period. There was a decrease in blood sugar in the third month of each therapy. Blood creatinine levels increased, thus evoking a renal pathology. A slight increase in transaminases levels was not significatif. Hematologic parameters were unchanged during the treatment and the histopathologic study showed hepatic glycogen decrease and a focal renal tube deterioration.

Administration, Oral↗
PubMed1998

[Analgesic and anti-inflammatory activity of saponins of Argania spinoza].

We studied analgesic and antiinflammatory actions of saponins of Argania spinosa cakes in mice and rats. With oral doses of 50 to 300 mg/kg, we found peripheric analgesic actions equivalent to the acetyl salicylic acid ones. The maximum protection was obtained with 500 mg/kg per os. There is no morphine-like central analgesic effect. Antiinflammatory studies were done in vivo using oedema due to carrageenine or experimental trauma in rats. There was a decrease in the paw swelling at doses of 10 mg/kg per os. At doses of 50 to 100 mg/kg per os, the antiinflammatory effect was similar to the one of indomethacin at doses of 10 to 20 mg/kg per os. In vitro, there was an inhibition of beef synovial fluid degradation by OH. radicals. The inhibition action is evaluated with an IC20 > or = 6 microM. Argania spinosa saponins have also an antiradical action against DPPH (IC25 = 85 mM) and against OH. radicals (IC25 = 0.56 M). Since they do not have any inhibition effect on PGE2 synthesis, their antiinflammatory activity can be explained by their action on leucotriens in the metabolic pathway of arachidonic acid.

Analgesics↗
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↗
PubMed1990

Effect of bromocriptine on neurogenic vasoconstriction in the isolated autoperfused hindquarters of the rat.

The effects of local administration of bromocriptine were studied in the isolated autoperfused hindquarters of the rat, and compared to the actions of apomorphine and pergolide. Local injection of bromocriptine (1 microgram kg-1) (into the hindquarters) did not alter perfusion pressure, but reduced the pressor response to electrical stimulation of the lumbar sympathetic chains at all frequencies used (0.5-10 Hz; 5 ms; 35 V). Bromocriptine (1 microgram kg-1) did not alter the increases in perfusion pressure induced by local administration of noradrenaline. The effects of local administration of apomorphine (1 microgram kg-1) and pergolide (1 microgram kg-1) were similar to that of bromocriptine. The inhibitory effect by bromocriptine, apomorphine and pergolide of the stimulation-evoked pressor responses was completely antagonized by intravenous administration of the dopamine receptor antagonist sulpiride (0.3 mg kg-1) but was not by the alpha 2-adrenoceptor antagonist yohimbine (1 mg kg-1). In this dose, yohimbine antagonized the inhibitory effect of the alpha-adrenoceptor agonist clonidine (1 microgram kg-1). The inhibitory effect of clonidine was not altered by sulpiride but was antagonized by yohimbine. The results indicate that bromocriptine like apomorphine and pergolide inhibit neurally-induced pressor responses in the autoperfused hindquarters of the rat by stimulation of presynaptic dopamine receptors. Stimulation of these receptors leading to a fall in noradrenaline release and consequently of vasomotor tone, might at least in part explain the vasodilatator effects of bromocriptine in the rat.

Animals↗
PubMed1990

Cardiovascular effects of bromocriptine in rats: role of peripheral adrenergic and dopaminergic receptors.

1. Experiments were designed to study the involvement of alpha-adrenoceptors and dopamine receptors in the hypotensive and bradycardic actions of bromocriptine in rats. 2. Intravenous administration of bromocriptine reduced blood pressure and heart rate which was inhibited by ganglionic blocking agents or by pithing. 3. The fall in blood pressure produced by bromocriptine was not modified by atropine, atenolol, prazosin, yohimbine, bilateral vagotomy or carotid ligation, but was blocked by sulpiride, domperidone and haloperidol. 4. The bradycardia produced by bromocriptine in intact rats was assumed to be mediated by the autonomic nervous system since it was partly reduced by bilateral vagotomy or atenolol, and entirely prevented by pithing. Furthermore, sulpiride but not yohimbine antagonized this effect. 5. In pithed rats, bromocriptine decreased both the pressor response (above 10 micrograms kg-1) and the tachycardia (above 50 micrograms kg-1) elicited by electrical stimulation of spinal cord outflow. Both effects were inhibited by sulpiride or yohimbine. 6. In pithed rats, bromocriptine did not affect the hypertension due to exogenous noradrenaline, phenylephrine, B-HT 920, nor the bradycardia evoked by stimulation of the cardiac muscarinic receptors by carbachol. 7. These results suggest that, in rats, bromocriptine produces hypotension via an action on presynaptic and/or ganglionic dopamine receptors, and causes bradycardia by activation of central dopamine receptors.

Anesthesia↗
PubMed1989

[Evaluation of the central anticholinergic activity of antidepressants. Comparison of two experimental methods].

The anticholinergic effect of atropine, imipramine, clomipramine and metapramine was evaluated on oxotremorine induced trembling in the mouse as well as on contractions of the isolated guinea pig ileum induced by electrical stimulation of the mesenteric plexus. The ED 50 and IC 50 which expressed the anticholinergic activity of these substances, were found to be identifically distributed for both methods. Activity, in decreasing order was found to be: atropine much greater than imipramine greater than clomipramine greater than metapramine. There was a good correlation between results from the two methods (r = 0.97). The method using the stimulated guinea pig ileum would therefore seem suitable for characterisation of potential anticholinergic activity of a molecule.

Animals↗
PubMed1988

Cardiovascular effects of etorphine in rats.

1. Cardiovascular effects of intravenously administered etorphine were investigated in mechanically ventilated normotensive rats under pentobarbitone anaesthesia. 2. Etorphine (0.1-2 micrograms kg-1) induced a dose-related bradycardia and hypotension which was prevented by pretreatment with naloxone (0.1 mg kg-1). 3. After bilateral vagotomy etorphine (1 microgram kg-1) produced a pressor effect which was prevented by prazosin (0.5 mg kg-1), but unaltered by adrenalectomy. 4. The bradycardia due to etorphine was abolished by bilateral vagotomy, but only partially reduced by atropine (1 mg kg-1) and still evident after propranolol (1.5 mg kg-1). 5. Etorphine was without effect on blood pressure in the pithed rat, although there was a small bradycardia which was not seen after naloxone. 6. The data presented indicate that etorphine produces an opioid receptor-mediated stimulation of both vagal (partially cholinergic) and sympathetic outflow and a direct cardiodepressant effect.

Adrenalectomy↗
PubMed1988

Dihydroergotoxine-induced bradycardia in rats.

Dihydroergotoxine (0.01-0.3 mg kg-1 i.v.) decreased heart rate in pentobarbitone-anaesthetized rats. The bradycardia was reduced but not blocked by pre-treatment with guanethidine, yohimbine, propranolol or pithing. It was not prevented by bivagotomy, atropine, sulpiride or haloperidol. Dihydroergotoxine failed to affect, either the bradycardia produced by electrical stimulation of the vagus, or the cardioacceleration induced by i.v. isoprenaline. The increase in heart rate elicited in pithed rats by electrical stimulation of the spinal cord was reduced by dihydroergotoxine; this effect being inhibited by yohimbine but not by sulpiride. In conclusion, the main mechanism by which dihydroergotoxine (i.v.) induces bradycardia in the rat involves stimulation of alpha 2-adrenoceptors located predominantly at the cardiac sympathetic nerve endings.

Animals↗
PubMed1987

Presynaptic inhibition by dihydroergotoxine of the response to peripheral sympathetic nerve stimulation in rats.

Dihydroergotoxine decreased the heart rate in both intact and pithed rats but increased blood pressure in pithed rats only. Dihydroergotoxine did not inhibit the postsynaptic effect of isoprenaline and noradrenaline but reduced the neurally induced pressor responses and tachycardia in the rat. The first effect was antagonized by sulpiride, and the second by yohimbine. It was concluded that dihydroergotoxine stimulates presynaptic alpha 2-adrenoceptors at the cardioaccelerator nerve endings, and presynaptic dopamine receptors at the sympathetic terminations innervating the vascular bed.

Animals↗
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↗
PubMed1987

Heart rate lowering effects of dihydroergotamine in rats.

Dihydroergotamine (10-100 micrograms/kg i.v.) decreased heart rate in pentobarbital anesthetized rats. This bradycardia was reduced but not blocked by guanethidine, yohimbine, propranolol, atropine, haloperidol, sulpiride, bivagotomy or pithing. In the pithed rat, dihydroergotamine failed to affect either the bradycardia produced by electrical stimulation of the vagus or the cardioacceleration evoked by i.v. isoproterenol, tyramine or aminophylline. The increase in heart rate elicited by electrical stimulation of the spinal cord was reduced by dihydroergotamine, this effect being blocked by yohimbine. In conclusion, in the rat, the main mechanism by which dihydroergotamine induces bradycardia involves stimulation of central and peripheral alpha 2-adrenoceptors. Via an action on these receptors, dihydroergotamine can inhibit the sympathetic outflow and enhance efferent vagal activity. This bradycardia may also reinforced by stimulation of central dopaminergic receptors and direct myocardial depression.

Animals↗
PubMed1986

Alpha 2-adrenergic agonist and alpha 1-adrenergic antagonist activity of ergotamine and dihydroergotamine in rats.

The effect of ergotamine and dihydroergotamine on peripheral alpha-adrenoceptors was examined in pithed rats. The pressor response to ergot alkaloids was reduced competitively by yohimbine but not by prazosin or methysergide. These results show that the vasoconstriction induced by ergot alkaloids is mediated by alpha 2-adrenoceptors. Ergot alkaloids decreased the tachycardia elicited by stimulation of the cardioaccelerator sympathetic nerves, this effect being antagonized by yohimbine. The pressor response to (-)-phenylephrine was reduced by ergot alkaloids, suggesting competitive antagonism. It is suggested that in the pithed rat both ergotamine and dihydroergotamine act at the periphery as competitive alpha 1-adrenoceptor blockers and partial alpha 2-adrenoceptor agonists.

Adrenergic alpha-Agonists↗
PubMed1986

Selectivity of raubasine stereoisomers for alpha 1- and alpha 2-adrenoceptors in the rat.

The selectivity of raubasine and its two isomers tetrahydroalstonine (THA) and akuammigine (AKU) for alpha 1- and alpha 2-adrenoceptors has been investigated in pithed normotensive rats. alpha 1-Adrenoceptor blockade was measured by inhibition of the pressor response to (-)-phenylephrine. alpha 2-Adrenoceptor blockade was measured by antagonism of the inhibitory effect of clonidine both on the tachycardia produced by electrical stimulation of the cardiac accelerator nerves and on the pressor response to B-HT 933. Pressor responses to (-)-phenylephrine were reduced in a dose-dependent manner by raubasine but not by THA and AKU. The inhibitory effect of clonidine and the pressor response to B-HT 933 were antagonized in a dose-dependent manner by THA but not by raubasine and AKU. These results indicate that, in pithed rats, AKU is a very weak antagonist at alpha 1- and alpha 2-adrenoceptors, raubasine is a preferential alpha 1-adrenoceptor antagonist, and THA is a selective alpha 2-adrenoceptor 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↗