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M Bourin

Publications and source records attributed to M Bourin.

At least 91 records · Page 5Linked to original sources
PubMed1996

Additive effects of glyburide and antidepressants in the forced swimming test: evidence for the involvement of potassium channel blockade.

Evidence in the literature suggests that the modulatory effects of antidepressant drugs (ADS) on neuronal excitability, via the inhibition of K+ channels, may be the final common pathway of pharmacological action. Therefore, we tested the hypothesis that combining the ATP-sensitive K+ channel blocker glyburide with a variety of ADS would produce an additive effect and decrease the immobility time of mice in the forced swimming test (FST). Glyburide (GLY, IP, 30 and 50 mg/kg) and subactive doses of ADS were administered 45 and 30 min, respectively, prior to behavioral testing. Results showed that when combined with GLY, ADS whose main pharmacological effect is one of 5-HT uptake blockade (imipramine, amitriptyline, citalopram, paroxetine, fluoxetine, and fluvoxamine) were more effective in decreasing the amount of time mice were immobile, than when these drugs were administered alone. Some noradrenaline uptake inhibiting ADS (desipramine and viloxazine, but not maprotiline) were also significantly more effective in decreasing immobility time when combined with GLY than when administered alone. Pretreatment with GLY was found to have no effect on the dopamine uptake inhibitor bupropion, and out of the atypical ADS tested (trazodone, mianserine and iprindole), only coadministration with iprindole decreased the immobility time. Only the specific MAO-A inhibitor moclobemide was observed to have an antiimmobility effect when combined with GLY. Neither MAO-B specific (RO 16 6491) nor mixed MAO inhibitors (nialamide and pargyline) interacted with GLY to produce antiimmobility effects. These results corroborate and extend our previous report of the ADS enhancing effects of quinine in the same behavioral model, and suggest that the additive effects of quinine and GLY on ADS in FST are a result of K+ channel blockade.

Animals↗
PubMed1996

A new design of trial for hypnotics comparison: a double-blind cross-over trial with patient's preference assessment and continuation of the preferred treatment.

1. This study compared two hypnotics administrated at comparable therapeutic dosages: triazolam (0.25 mg) and loprazolam (1 mg), were administered using an original scheme (cross-over on the first 2 nights, and continuation of the preferred treatment or new randomization). 2. Sixty-seven outpatients complaining of common insomnia participated in this study conducted by general practitioners. 3. Both drugs provided improvement in sleep quality (decreased sleep latency, increased total duration of sleep, decreased number of night awakenings), and are equally well tolerated. 4. For the first 2 nights, triazolam was evaluated to be more efficient than loprazolam (p < 0.001), and patients felt more rested the following day (p < 0.01) with the former drug. Moreover, triazolam is more frequently preferred than loprazolam by 47.7% and 29.2%, respectively, (p = 0.09). 5. No interaction was found between treatment and order of administration or specific effects and order of administration.

Adult↗
PubMed1996

The future of antidepressants.

A common action of many antidepressants is the inhibition of the reuptake of the biogenic amines norepinephrine, serotonin (5-HT) and/or dopamine into nerve terminals. Another postulated mechanism of action for many antidepressants is the downregulation of beta-adrenergic receptors postsynaptically after chronic administration. Many antidepressants have been reported to produce changes in the regulation of 5-HT1 and 5-HT2 receptors chronically. None of these mechanisms is completely satisfactory as a common antidepressant mechanism of action. Is it possible to unify these hypotheses of antidepressant action? A number of receptor changes have been recognized in depression. Usually, these implicated receptors are linked to a G protein. Thus, it could be hypothesized that depression may be the result of a disorder of the large family of receptor-linked G proteins. Depression, a disorder in which there seems to be an important genetic component, could be expressed in either the receptor or in the G proteins, leading to a defective linkage between the receptor and the G protein, resulting in abnormal transduction mechanisms. The concept of antidepressants is changing rapidly as these agents appear with new therapeutic indications other than depression, such as panic disorder, obsessive compulsive disorder, etc. It can be expected that the presently available antidepressants might eventually be considered anxiolytics or that benzodiazepines and 5-HT1A agonists could come to be viewed as disinhibiting substances.

Antidepressive Agents↗
PubMed1996

Differential effects of clonidine, lithium and quinine in the forced swimming test in mice for antidepressants: possible roles of serotoninergic systems.

The forced swimming test (FST) is a behavioral test used to predict the efficacy of antidepressant (AD) treatments. In the present study, it was found that, when combined with clonidine, lithium or quinine, subactive doses of several types of ADs (tricyclics, 5-HT uptake inhibitors and atypical ADs) produced anti-immobility effects in mice. Clonidine (0.06 mg/kg) was found to potentiate the AD-like effects of all the drugs tested in the FST. More interesting is the additivity of gepirone with lithium (1 mEq/l), and ondansetron with quinine (0.5 mg/kg). The results of the present study are in favour of the potentiation of AD activity by clonidine via 5-HT2 receptors, lithium through 5-HT1A receptors, and quinine through 5-HT3 receptors. Further studies to examine in detail which of these three 5-HT receptors or their subtypes is the most important in the actions of individual ADs are warranted.

Animals↗
PubMed1996

Nitric oxide mediates caerulein-induced suppression of locomotor activity.

Caerulein, a non-selective agonist of cholecystokinin (CCK) receptors, is shown to suppress locomotor activity in rodents via stimulation of CCK(A) receptors. In the present study we examined the possible involvement of nitric oxide (NO) in caerulein-induced hypolocomotion in rats. Caerulein (10 microg/kg) markedly decreased the horizontal and vertical components of locomotor activity in rats measured in dark motility boxes. Pretreatment with a nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), at 5 mg/kg i.p., abolished the inhibiting action of caerulein on the horizontal activity, but did not affect the reduced frequency of rearing. The other doses of L-NAME (1, 10 and 20 mg/kg) were ineffective against caerulein. As L-NAME at this dose range does not stimulate locomotor activity, it is likely that NO is involved in the motor suppressant effect of systemically administered caerulein.

Analysis of Variance↗
PubMed1996

A schematic representation of the psychopharmacological profile of antidepressants.

1. Using simple animal tests, "behavioural" and "biochemical" aspects of depression, anxiolysis, disinhibition, psychostimulation and sedation were investigated in mice using a variety of antidepressant drugs. 2. Dothiepin and mianserin (16 and 32 mg/kg), fluoxetine (32 and 64 mg/kg), maprotiline and imipramine (16, 32 and 64 mg/kg) and viloxazine (16 mg/kg) significantly potentiated mortality following acute administration with yohimbine. 3. Dothiepin and imipramine (32 mg/kg), fluoxetine (16 and 32 mg/kg), viloxazine (8 and 16 mg/kg), maprotiline (32 mg/kg) and mianserin (32 mg/kg) reduced immobility time in the forced swimming test. 4. In the black and white box, dothiepin (32 mg/kg) significantly increased the time spent in the bright compartment: Fluoxetine (8 and 16 mg/kg) significantly increased the number of crossings between compartments, an effect indicative of desinhibition. 5. It can be concluded that dothiepin possesses both antidepressant and anxiolytic properties in these animal models. The present procedure is useful not only for the screening of compounds that may possess antidepressant properties, but is also of value in determining other properties that may contribute to the overall clinical efficacy of the drugs.

Adrenergic alpha-Antagonists↗
PubMed1996

Two faces of cholecystokinin: anxiety and schizophrenia.

It has been suggested that cholecystokinin (CCK), a gut-brain peptide found in high concentrations in the mammalian brain, might be implicated in the neurobiology of anxiety and panic disorder. The administration of CCK tetrapeptide induced panic attacks analogous to spontaneous ones in patients suffering from panic disorder and to a lesser degree in healthy volunteers. In animal models of anxiety, the pretreatment with CCK agonists and antagonists produced, respectively, anxiogenic- and anxiolytic-like action on the exploratory paradigms. On the other hand, CCK could also play a role in the pathophysiology of schizophrenia. The administration of CCK agonists (caerulein, CCK-8s) to rodents results in behavioural effects analogous to those of antipsychotic drugs. However, CCK agonists lack any activity in rodent behavioural models to reveal antipsychotic drugs. A significant reduction of CCK concentration and CCK receptors has been shown in cortical and limbic structures of patients suffering from schizophrenia. Nevertheless, administration of CCK agonists to these patients does not effect their symptoms. Two major conclusions should be drawn: first, CCK is involved in the neurobiology of anxiety; second, changes in the CCK system in schizophrenia could be linked to a cortical neurodegeneration related to this disease.

Animals↗
PubMed1996

5-HTP induced diarrhea as a carcinoid syndrome model in mice?

Serotonin (5-HT) is present in the gastrointestinal tract and is probably one of the compounds responsible for diarrhea in patients presenting with carcinoid syndrome. Intraperitoneal administration of L-5-hydroxytryptophan (L-5-HTP) at doses of 25 to 100 mg/kg dramatically increase defecation in mice. In this new paradigm, counting fecal boli deposited is simple and the appraised or inhibition of diarrhea induced by ip 25 mg/kg of L-5-HIP is very clear, with a good reproducibility of scores. L-5-HTP needs to be metabolized into 5-HT to be active; benserazide, an inhibitor of decarboxylase, antagonized the diarrhea induced by 5-HT. Among the 5-HT antagonists used in interaction with 5-HT, only these of the 5-HT3 type (ondansetron, granisetron, tropisetron) and, to a lesser extent 5-HT2 type (ritanserin), decreased the diarrhea induced by 5-HTP. The 5-HT4 receptor agonists from the benzamide family (metoclopramide and zacopride) increased defecation in mice but the effect failed to reach statistical significance.

5-Hydroxytryptophan↗
PubMed1996

The effect of the potassium channel activator, cromakalim, on antidepressant drugs in the forced swimming test in mice.

The forced swimming test (FST) is a widely used behavioural model to predict potential antidepressant (AD) action of compounds in humans. It has been previously shown that pretreatment with lithium, quinine and clonidine had additive effects on AD drugs in the FST, an effect proposed to be a result of potassium channel blockade. It is possible that pretreatment with potassium channel openers may induce opposite effects to those seen following pretreatment with potassium channel blockers in the FST. Pretreatment with cromakalim (CROM) (1 mg/kg, intraperitoneally [i.p.]) antagonized the anti-immobility effect of the mixed noradrenaline (NA)/5-hydroxytryptamine (5-HT) reuptake inhibitors imipramine and amitriptyline (P < 0.05). CROM administration (0.06 and 1 mg/kg, i.p.) also blocked the AD-like effects of the specific NA reuptake inhibitor, desipramine, and the selective serotonin reuptake inhibitor, paroxetine (P < 0.05 and P < 0.01, respectively). Pretreatment with CROM via gavage (1 mg/kg) antagonized the AD-like effects of imipramine, amitiptyline, desipramine and paroxetine. CROM treatment (via i.p. route or gavage) did not have any significant effect on the anti-immobility activity of the atypical AD mianserin at any of the doses employed. Another potassium channel opener, minoxidil (MINOX), which does not cross the blood-brain barrier, was also tested to eliminate the possibility that CROM may be acting via peripheral/local mechanisms. MINOX (32 mg/kg) failed to antagonize anti-immobility effects of any of the AD tested. In conclusion, the results of the present study suggest that CROM is only acting on drugs involved with neurotransmitter uptake inhibition.

Amitriptyline↗
PubMed1996

[Effects of temperature and PH on dissolution kinetics of methotrexate in aqueous media].

In vitro dissolution kinetics of Methotrexate have been analysed at different temperatures in water at pH 1.5. After giving rise to the dissolution reaction, it has been possible to follow up the kinetic of dissolution and calculate energy activation. The pH variation allows us also to appreciate the constant behaviour of dissolution at temperature 310 K (37 degrees). Weilbull equation is valid with success for dissolution reaction as well during temperature variation and different values of pH. In both cases the Weibull constant b has been calculated and compared to constant dissolution K.

Hydrogen-Ion Concentration↗
PubMed1996

[From inducers of panic attack to neurobiology of panic disorder].

Various provocative agents, including sodium lactate, carbon dioxide (CO2), caffeine, yohimbine and cholecystokinin (CCK), have been utilized as panicogenics in studies on healthy volunteers as well as in panic disorder patients. Most provocative agents are lacking in specificity, limiting their use in identifying neurotransmitter systems involved in panic attacks. CCK appears to offer several advantages over other challenge strategies since it is a putative neurotransmitter in the CNS, with its own neuronal pathways and receptors, and reliably provokes panic attacks in a dose-dependent manner. It is important to clarify the relationships between CCK and other neurotransmitter systems in order to further understand the neurobiology of panic disorder. The possible roles of some of these neurotransmitters in panic disorder are discussed in this review.

Arousal↗
PubMed1995

Inhibition of nitric oxide synthase causes anxiolytic-like behaviour in an elevated plus-maze.

The action of inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME) (1-20 mg kg-1) on the exploratory behaviour of rats in the elevated plus-maze was studied. L-NAME induced an anxiolytic-like effect in the plus-maze test, showing a reverse U-shape action behaviour, with a maximal effect at 10 mg kg-1. This effect was not related to a non-specific increase in motor activity, since in the open field test L-NAME did not affect locomotor activity of rats. Pretreatment of rats with L-NAME (1-10 mg kg-1) also tended to attenuate the anti-exploratory action of CCK agonist caerulein (5 micrograms kg-1), but this action was not significant. In conclusion, it appears that NO may be involved in the process that can lead to anxiety in the rat.

Animals↗
PubMed1995

Role of N-methyl-D-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats.

We studied the aggressive behaviour induced by repeated treatment with apomorphine, a dopamine agonist (0.5 mg/kg s.c. twice daily, 10 days), in rats. The first signs of defensive aggressiveness appeared on the third day of apomorphine treatment and were generally seen on the 7th day. Aggressiveness induced by a challenge dose of apomorphine (0.5 mg/kg s.c.) on the 11th day was antagonized by haloperidol (0.05 and 0.1 mg/kg i.p.) and clozapine (10 mg/kg i.p.). An antagonist of N-methyl-D-aspartate (NMDA)-gated channels, dizocilpine (MK-801), also blocked the aggressive behaviour at 0.25 and 0.5 mg/kg i.p. but caused ataxia. When dizocilpine (0.25 mg/kg i.p.) and apomorphine were coadministered for 10 days, aggressive behaviour did not develop. At 0.025 mg/kg i.p., dizocilpine even accelerated the appearance of apomorphine-induced aggressive behaviour, which manifested on the 3rd day in all rats. In a separate study, a 7-day treatment with dizocilpine (0.25-1 mg/kg i.p.) of rats, sensitized by a prior 10-day apomorphine treatment, did not reverse the established aggressive behaviour. The coadministration of apomorphine and cholecystokinin (CCK) -A or -B antagonists, devazepide or L-365,260 (0.01-2.5 mg/kg i.p.) respectively, neither affected development of apomorphine-induced aggressive behaviour nor intensity of aggressiveness in the sensitized rats. In binding studies neither density nor affinity of striatal dopamine D2 receptors was changed by acute or chronic apomorphine treatment. The number of [3H]pCCK-8 binding sites in the frontal cortex increased already after a single injection of apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗
PubMed1995

The additive effects of quinine on antidepressant drugs in the forced swimming test in mice.

The aim of this study was to investigate if quinine plus antidepressant drugs (ADS) leads to an additive effect in the forced swimming test. Quinine (0.125, 0.5 mg/kg) and ADS (subactive doses) were given IP 45 and 30 min, respectively, before the test. When combined with QUIN, all drugs that act via inhibition of 5-HT uptake (imipramine, amitriptyline, citalopram, paroxetine, fluoxetine and fluvoxamine) significantly increased the swimming time of mice. Among trazodone, mianserin and iprindole (atypical ADS), only iprindole combined with quinine decreased the immobility (increased swimming) of the animals. The specific noradrenaline (NA) uptake inhibitors, desipramine and viloxazine, but not maprotiline, were also found to reduce the immobility time when pretreated with quinine. The mixed monoamine oxidase (MAO) inhibitor (pargyline) and MAO-A inhibitor (moclobemide) also shortened the period of immobility whereas the MAO-B inhibitor (nialamide) and the dopamine (DA) uptake inhibitor (bupropion) did not. Quinine's additive effects on several types of ADS is likely a result of blockade of potassium channels.

Animals↗
PubMed1995

Controlled comparison of the effects and abrupt discontinuation of buspirone and lorazepam.

1. The purpose of this study was to compare the effects and abrupt discontinuation of buspirone 15 or 20 mg tid and lorazepam 3 or 4 mg tid following 8 weeks of treatment. A total of 43 outpatients with generalized anxiety disorder were included in the study and 39 entered the withdrawal phase. 2. Clinical assessments were performed at baseline, 2, 4, 6 and 8 weeks (active phase) and after 9 and 10 weeks (withdrawal phase). These included the Hamilton anxiety scale, the visual analogue scale, the CHESS 84 (a check list for the evaluation of somatic symptoms) and the Lader tranquilizer withdrawal scale (translated in french). 3. Results show similar efficacy for lorazepam and buspirone during the active phase with a higher significant difference for buspirone on the CHESS 84 in relation with neurovegetatives symptoms: lorazepam D0 :16.30 +/- 3.14 D56: 5.10 +/- 0.93 (p < or = 0.01) buspirone D0 :18.82 +/- 3.4 D56: 4.73 +/- 1.18 (p < or = 0.001) No withdrawal phenomena was observed for both drugs using HAM-A lorazepam D63 :12.59 +/- 2.26 D70: 12.0 +/- 1.75 (p = ns) buspirone D63 :10.05 +/- 1.28 D70: 10.32 +/- 1.82 (p = ns) and the same significant difference using Lader scale: lorazepam D63 :4.44 +/- 0.89 D70: 6.96 +/- 1.28 (p < or = 0.05) buspirone D63 :2.95 +/- 0.66 D70: 4.15 +/- 0.92 (p < or = 0.05). 4. This study confirmed that buspirone was as effective as lorazepam at D56 in monitored outpatients with generalized anxiety disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Sigma ligand S14905 and locomotor activity in mice.

The binding and locomotor profile of a new sigma ligand, S14905, (isobutyl-N-(1-indan-2yl-piperid-4-yl)N-methyl carbamate, furamate) was studied. The binding data revealed that S14905 has a high affinity for sigma receptors and very low affinity for both dopamine D1 and D2 receptors. We have demonstrated that this sigma ligand prevents the locomotor stimulation induced by morphine (32 and 64 mg/kg), cocaine (16 mg/kg), amphetamine (4 mg/kg) and adrafinil (32 mg/kg) at doses lower than those required to depress spontaneous locomotor activity. The antagonism observed in the present study seems to be more specific of morphine induced hyperlocomotion. The high affinity of this compound for sigma receptors makes it a good choice to study the role of this receptor in the CNS. In addition, S14905 does not directly block dopamine receptors but may modulate them in some manner, and would thus warrant further study as a potential atypical antipsychotic agent, and an antagonist for the hyperactivity induced by opiate drug.

Amphetamine↗
PubMed1995

[Experimental and clinical pharmacology of psychostimulants].

OBJECTIVE: To examine the fact that, after 50 years, the introduction of amphetamines for therapeutic purposes, psychostimulants such as methylphenidate have proved to be effective medications used in the treatment of childhood hyperactivity, yet misunderstood. METHOD: A review of the literature is undertaken on the use of psychostimulants in children and adults. RESULTS: Studies evaluating their helpfulness in adults are for the most part outdated and nonexploratory. CONCLUSION: their rehabilitation could prove to be useful for young and older adults, on condition that their target syndromes are studied more thoroughly.

Adult↗