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Biomedical subjects

M Boucard

Publications and source records attributed to M Boucard.

At least 19 recordsLinked to original sources
PubMed1996

Maternity and medicinal plants in Vanuatu. II. Pharmacological screening of five selected species.

An ethnobotanical survey of reproductive behaviour in Vanuatu and an extensive literature search have resulted in the selection of five plant species (Asplenium nidus, Hemigraphis reptans, Homalanthus nutans, Dysoxylum gaudichaudianum, Pemphis acidula) used for purposes relating to human reproduction in that country. Preliminary screening was carried out to identify possible oestrogenic activity in these species as well as their effects on isolated rat uteri. Dysoxylum gaudichaudianum presented the most interest due to its spasmolytic activity (musculotropic type). Its mode of action has yet to be determined.

Animals↗
PubMed1996

Smooth muscle relaxant activity of A1- and A2-selective adenosine receptor agonists in guinea pig trachea: involvement of potassium channels.

The relaxant activities of N6-cyclopentyladenosine (CPA), an A1-selective agonist, and of 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), a potent A2-receptor agonist, in the carbachol-contracted guinea pig isolated trachea have been evaluated. Both CPA and CPCA induced concentration-dependent relaxations of the guinea pig trachea, CPCA demonstrating a more potent but less efficient activity. 8-Cyclopentyl-1,3-dimethylxanthine (CPT) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (10 microM), both selective and potent A1-adenosine receptor antagonists, induced only a weak inhibition of CPA while 3,7-dimethyl-1-propargylxanthine (DMPX) (10 microM), a selective A2-adenosine receptor antagonist, failed to antagonize the relaxant activity of CPA. These results indicate that a major component of the tracheal relaxant activity of CPA occurred by a mechanism which is insensitive to the antagonist potency of A1- and A1-xanthine adenosine antagonists and therefore was not mediated by A1- or A1-adenosine receptors activation. The relaxant activity of CPCA was inhibited by DMPX, which supported the involvement of A2-adenosine receptors. Glibenclamide (10 microM), an inhibitor of KATP-channels, inhibited the relaxant activity of CPCA, whereas it was without effect on CPA. Iberiotoxin (180 nM), an inhibitor of the large-conductance CA2(+)-activated K+ channel, inhibited the relaxant action of CPA and CPCA. However, verapamil can offset the inhibition of CPA provided by iberiotoxin which suggests that such an antagonism does not represent an interaction between the toxin and CPA at the level of the large-conductance CA2(+)-activated K(+)-channel gating but rather functional antagonism attributable to the promotion of CA2+ influx by the toxin. In contrast, verapamil only partially reversed the inhibition of CPCA relaxant activity provided by iberiotoxin. Taken together, these results suggest that A2-adenosine receptor subtypes are coupled to KATP-channels and large-conductance CA2(+)-activated K(+)-channels in the guinea pig trachea whereas the unidentified adenosine receptor subtype, involved in CPA relaxant activity, is not.

Adenosine↗
PubMed1995

Pharmacological activities of imidazo[1,2-alpha]pyrazine derivatives.

The smooth muscle relaxant activity and other pharmacological properties of imidazo[1,2-alpha]pyrazine derivatives were compared with those of theophylline. Imidazo[1,2-alpha]pyrazine derivatives exhibited a potent smooth muscle relaxant activity regardless of the agent which had elicited the contraction and thus showed a broad spectrum of non specific smooth muscle relaxant activity. In the isolated guinea-pig atria, imidazo[1,2-alpha]pyrazine derivatives exhibited potent inotropic and chronotropic activities. As opposed to theophylline, the imidazo[1,2-alpha]pyrazine derivatives tested were unable to antagonize the adenosine-induced inhibition of spontaneous contractile activity of rabbit ileum. Furthermore, as opposed to theophylline, these derivatives did not exhibit a marked diuretic activity. Thus it appears that they do not act as adenosine receptor antagonists. Imidazo[1,2-alpha]pyrazine derivatives inhibited the total cAMP-phosphodiesterase (cAMP-PDE) and the total cGMP-phosphodiesterase (cGMP-PDE) activities of bovine trachea but with relatively low potencies, sharing a discrepancy between their activity on isolated tissues and their ability to inhibit PDE. It is suggested that imidazo[1,2-alpha]pyrazine derivatives may selectively inhibit type III and/or type IV phosphodiesterase isoenzymes involved in the regulation of the mechanical activity of cardiac and smooth muscle tissues.

Adenosine↗
PubMed1993

Evaluation of the relaxant effects of SCA40, a novel charybdotoxin-sensitive potassium channel opener, in guinea-pig isolated trachealis.

1. Experiments have been performed in order to analyse the mechanism whereby SCA40, a new imidazo[1,2-a]pyrazine derivative relaxes airway smooth muscle. 2. SCA40 (0.01-10 microM) caused a complete and concentration-dependent relaxation of guinea-pig isolated trachea contracted with 20 mM KCl but failed to inhibit completely the spasmogenic effects of 80 mM KCl. 3. Quinine (30 microM) antagonized the relaxant activity of SCA40 in 20 mM KCl-contracted guinea-pig isolated trachea. The ATP-sensitive K(+)-channel blocker, glibenclamide (3 microM), did not antagonize the relaxant activity of SCA40 in either 20 mM KCl or 1 microM carbachol-contracted isolated trachea. 4. SCA40 (0.01-10 microM) and isoprenaline (0.1 nM-10 microM) caused a complete and concentration-dependent relaxation of guinea-pig isolated trachea contracted with carbachol 1 microM. 5. The large-conductance Ca(2+)-activated K(+)-channel blocker, charybdotoxin (60-180 nM), non-competitively antagonized the relaxant activity of isoprenaline on 1 microM carbachol-contracted trachea. The inhibition was characterized by rightward shifts of the isoprenaline concentration-relaxation curves with depression of their maxima. 6. The relaxant activity of SCA40 in 1 microM carbachol-contracted trachea was antagonized by charybdotoxin (60-600 nM) in an apparently competitive manner. The concentration-relaxation curves to SCA40 were shifted to the right with no significant alteration in the maximum response. 7. It is concluded that SCA40 is a novel potassium channel opener which is a potent relaxant of guinea-pig airway smooth muscle in vitro. The relaxant activity of SCA40 does not involve ATP-sensitive K+-channels but rather large-conductance Ca2'-activated K+-channels or other charybdotoxin sensitive K+-channels.

Animals↗
PubMed1993

Cardiovascular effects of SCA40, a novel potassium channel opener, in rats.

1. Experiments have been performed to investigate the cardiovascular actions in the rat of SCA40, a novel potassium channel opener which is a potent relaxant of guinea-pig airway smooth muscle in vivo and in vitro. 2. SCA40 (0.01-30 microM) caused a complete and concentration-dependent relaxation of rat isolated thoracic aorta contracted with 20 mM KCl but failed to inhibit completely the spasmogenic effects of 80 mM KCl. 3. The ATP-sensitive K(+)-channel blocker, glibenclamide (3 microM), failed to antagonize the relaxant action of SCA40 on 20 mM KCl-contracted rat isolated thoracic aorta. 4. SCA40 (0.001-100 microM) had dual effects on rat isolated atria. At low concentrations, SCA40 produced a concentration-dependent decrease in the rate and force of contractions. At higher concentrations (greater than 1 microM) SCA40 induced concentration-dependent increases of atrial rate and force. 5. In vivo, in normotensive Wistar rats, SCA40 elicited a dose-dependent (1-100 micrograms kg-1) decrease in mean arterial pressure which was accompanied by a moderate dose-dependent increase in heart rate. SCA40 (100 micrograms kg-1) had a slightly greater hypotensive effect than cromakalim (100 micrograms kg-1) but the duration of the hypotension was longer with cromakalim than with SCA40. 6. The hypotensive effect of SCA40 was not reduced by propranolol, atropine, NG-nitro-L-arginine methyl ester (L-NAME) or glibenclamide. 7. It is concluded that the mechanism by with SCA40 relaxes vascular smooth muscle in vitro and in vivo involves activation of K(+)-channels distinct from glibenclamide-sensitive ATP-sensitive K(+)-channels.

Animals↗
PubMed1993

[Effects of toxins, apamine, charybdotoxin and iberiotoxin on the relaxation of the smooth muscular fiber induced by imidazo(1,2-a)pyrazine derivative].

Experiments have been performed in order to analyse the mechanism whereby SCA40, a new imidazo[1,2-a]pyrazine derivative relaxes airway smooth muscle. We investigated the effect of different toxins, known to be K(+)-channel blockers on guinea-pig smooth muscle relaxant activity of SCA40. The small conductance Ca(2+)-activated K(+)-channel blocker apamin (100 nM) did not antagonize the relaxant activity of SCA40 in 1 microM carbachol-contracted isolated guinea pig trachea. The large conductance Ca(2+)-activated K(+)-channel blocker, iberiotoxin (30, 60 and 180 nM) antagonized the relaxant activity of SCA40 in an apparently competitive manner. The concentration-relaxation curves to SCA40 were shifted to the right with no significant alteration in the maximum response. The relaxant activity of SCA40 in 1 microM carbachol-contracted isolated trachea was antagonized by both charybdotoxin (60 nM) and iberiotoxin (60 nM), but the antagonism induced by iberiotoxin appears to be more potent than that induced by charybdotoxin. It is concluded that the potent relaxant activity of SCA40 on guinea-pig airway smooth muscle in vitro involves a charybdotoxin and iberiotoxin sensitive K(+)-channel.

Animals↗
PubMed1992

Synthesis and antibronchospastic activity of 8-alkoxy- and 8-(alkylamino)imidazo[1,2-a]pyrazines.

Theophylline still occupies a dominant place in asthma therapy. Unfortunately its adverse central nervous system (CNS) stimulant effects can dramatically limit its use, and adjustments in the dosage are often needed. We have synthesized a new series of imidazo[1,2-alpha]pyrazine derivatives which are much more potent bronchodilators than theophylline in vivo and do not exhibit the CNS stimulatory profile. In vitro studies on isolated rat uterus and guinea pig trachea confirm the high potentialities of these derivatives. 6-Bromo-8-(methylamino)imidazo[1,2-alpha]-pyrazine-3-carbonitrile (23) is identified as the most potent compound of the series. As in the case of theophylline, phosphodiesterase inhibition appears unlikely to be the unique mechanism of action of this series of heterocycles.

Animals↗
PubMed1990

The use of Gd-DOTA in magnetic resonance imaging of experimentally induced mammary tumors.

Gd-DOTA contrast enhancement of MR images was evaluated on induced mammary tumors in female rats. A single intravenous injection of the carcinogenic N-nitrosourea ENU was administered to Wistar rats; this simple treatment led to a high percentage of mammary tumors without causing death. All the induced tumors were adenocarcinoma and their heterogeneousness depended on their size. The induced tumors did not have intra- or extravascular inflammatory spaces caused by heterotopic lesions, as is the case with implanted tumors. Before injection of Gd-DOTA, appearance of the patchy internal structure was clearly demonstrated on spin-echo images performed with long repetition times. Three doses of the paramagnetic contrast agent (0.1, 0.2, and 0.5 mmol/kg) were evaluated on two different T1-weighted MR sequences. Images were recorded before and repeatedly after intravenous injection of Gd-DOTA, and signal intensities and relaxation times were measured. On images acquired with the spin-echo 500/28 as well as the inversion-recovery 928/26/300 sequences, the results showed that 0.2 mmol/kg Gd-DOTA was the optimal dose for contrast enhancement and for clear visualization of the heterogeneousness of the mammary tumor.

Adenocarcinoma↗
PubMed1989

Synthesis and contractile activity of new acetylenic and allenic analogues of leukotrienes C4 and D4: importance of the Z-11,12 double bond.

The (5S,6R) isomers of new acetylenic and allenic analogues of leukotrienes C4 and D4 were synthesized for comparative pharmacological studies on intestinal smooth muscle preparations. These new analogues are poor spasmogenic agonists, the replacement of the 11,12-ene with a relatively more stable triple bond causing an important reduction in intrinsic activity. They did not show any significant antagonist activity. Unexpectedly, these results prove that the 11,12 portion in the triene structure of the lipophilic chain is critical for an agonist activity.

Animals↗
PubMed1988

Post-natal evolution of rat cardiac beta-adrenoceptors.

Cardiac beta-adrenoceptors (beta AR) were studied using membranes prepared at birth (day 0) and at days 7, 10, 15, 21, 30, 45 and 60. Saturation experiments using the antagonist ligand (125I)-iodocyanopindolol (ICYP) allowed the determination of beta AR number (Bmax) and ICYP dissociation constant (Kd), while (-)isoproterenol competition curves of ICYP binding, performed in the absence or presence of Gpp(NH)p (10(-4) M), were used to measure the relative proportions of high and low affinity states of the beta AR for the agonist and to assess the ability of beta AR to couple with the GTP-binding protein. Rat cardiac beta AR evolved at 3 distinct periods: during the first period (days 0-10), the receptor density and ICYP Kd were half that of adults, and beta AR were present only in an homogeneous high affinity state. The second period (days 15-21) was characterized by a progressive increase in beta AR number and ICYP Kd, while analysis of (-)isoproterenol competition curves indicated that beta AR were poorly coupled to the GTP-binding protein. In the third period (days 30-60), ICYP Bmax and Kd were respectively 53.9 +/- 1.2 fmoles/mg protein and 106.4 +/- 2.9 pM, while analysis of (-)isoproterenol competition curves showed the existence of high and low affinity binding states in equal proportions in the absence of Gpp(NH)p, and of one homologous low affinity state of the receptor in its presence. These data indicate that beta AR follow a postnatal evolution marked by an increase in beta AR density concomitant with a decrease in affinity toward the antagonist ligand ICYP, accompanied by the progressive appearance of a poorly-coupled beta AR. However, the number of efficiently coupled receptors was found to be similar in adult and newborn rats.

Animals↗
PubMed1984

Circadian changes in carrageenin-induced edema: the anti-inflammatory effect and bioavailability of phenylbutazone in rats.

The circadian variations in paw-edema produced by carrageenin and the anti-inflammatory effect of phenylbutazone were studied, in rats kept under a 12 light-12 dark regimen, in comparison with the variations of plasma phenylbutazone and oxyphenbutazone levels. When the experiment was performed during the light span (08.00 and 14.00 h), the rats were highly sensitive to the phlogistic effect of carrageenin, the plasma levels of phenylbutazone and oxyphenbutazone were lower, and the anti-inflammatory effect of phenylbutazone, weaker. Opposite results were obtained when the experiment was performed during the dark span (02.00 and 20.00 h). The results indicate that the chronoeffectiveness of phenylbutazone is influenced by both its chronokinetics and the chronesthesy of the biosystem involved.

Animals↗
PubMed1984

Synthesis of imidazo[1,2-a]pyrazine derivatives with uterine-relaxing, antibronchospastic, and cardiac-stimulating properties.

A series of imidazo[1,2-alpha]pyrazine derivatives was synthesized by condensation of alpha-halogenocarbonyl compounds and aminopyrazines. Various compounds resulted from competitive reactions or reagent isomerization and demonstrated in vitro uterine-relaxing and in vivo antibronchospastic activities. On isolated atria, 5-bromoimidazo-[1,2-alpha]pyrazine showed positive chronotropic and inotropic properties; the latter was associated with an increase in the cyclic AMP tissue concentration. Potentiation of the isoproterenol positive inotropic effect of 5-bromoimidazo[1,2-alpha]pyrazine and the lack of blockade of the 5-bromoimidazo[1,2-alpha]pyrazine positive inotropic effect by propranolol suggested phosphodiesterase-inhibiting properties.

Animals↗
PubMed1983

Circadian and circannual variation of the carrageenin inflammatory effect in rat.

The circadian variation of edema produced by carrageenin (carr.) administration into plantar tissue was studied in rats kept under a 12 light - 12 dark regimen. Three doses were used (125, 250 and 500 micrograms per rat) injected at different time (02.00, 08,00, 14.00 and 20.00 h). With the high doses, the level of edema for the four hour period after carr. administration was similar whatever the hour of injection. In contrast, with the lower dose (125 micrograms) a circadian rhythm in the intensity of the edema produced was observed, showing a maximum of susceptibility during the light span. Repetitive experiments performed at different periods of the year validated this finding. Comparing mean mesors, analysis of this data showed two distinct levels of inflammation, with the lower level observed in autumn and winter indicating evidence for a circannual variability.

Animals↗
PubMed1981

[Comparative hepatic toxicity of perhexiline maleate and griseofulvin in mice].

Hepatic toxicity was observed in mice which had received Griseofulvin or Perhexilin Maleate over a period of several months. Treatment of griseofulvin alone gave rise to hepatitis with the presence of Mallory bodies (MB) whereas the same length of treatment with Perhexilin Maleate was associated with steatonecrosis with an absence of MB. When treatment was followed by a one month rest period hepatic lesions disappeared with no trace of sequelae. Cross-treatment studies showed that one week of Perhexiline Maleate was sufficient to induce MB in mice pretreated with Griseofulvin. Similarly, Griseofulvin administered to mice pretreated with Perhexilin Maleate gave rise to MB formation after one week as opposed to the usual two months incubation time (DENK et al.). The histological nature and mode of formation of these MB was identical to that encountered in acute alcoholic hepatitis. On addition, combined drug therapy employing Perhexilin Maleate suggests a particular hepatic toxicity in man in cases where the liver has become predisposed due to other therapeutic.

Animals↗