La cholecystokinine (CCK) a d'abord ete identifiee comme etant un peptide du systeme gastro-i... more La cholecystokinine (CCK) a d'abord ete identifiee comme etant un peptide du systeme gastro-intestinal avant qu'il ne soit mis en evidence au niveau du cortex cerebral. Son activite s'exprime grâce a deux types de recepteurs CCK A et CCK B . Des etudes chez l'homme ont montre que l'injection du tetrapeptide, la CCK 4 , induisait des attaques de panique aussi bien chez des volontaires sains que chez des patients presentant un trouble panique. Ces derniers se montrant plus sensibles que les volontaires sains a l'injection de CCK 4 CCK 4 s'avere donc un agent inducteur des attaques de panique au meme titre que le CO 2 ou le lactate. Du fait de sa presence physiologique dans le cerveau humain la question est posee de connaitre le role de la CCK dans la neurobiologie de l'anxiete.
The forced swimming test (FST) in mice has failed to predict antidepressant activity for drugs ha... more The forced swimming test (FST) in mice has failed to predict antidepressant activity for drugs having beta adrenoreceptor agonist activity and for serotonin uptake inhibitors. We investigated the potential for clonidine to render the FST sensitive to antidepressants by using a behaviorally inactive dose of this agent (0.1 mg/kg). All antidepressants studied (tricyclics, 5-HT uptake inhibitors, iprindole, mianserin, viloxazine, trazodone) showed either activity at lower doses or activity at previously inactive doses. The effect appeared specific because it did not appear with drugs other than antidepressants (diazepam, chlorpromazine, sulpiride, atropine), except for amphetamine and apomorphine which have a strong effect on the dopaminergic system. The use of behaviorally subactive doses of clonidine may thus provide an important means of increasing the sensitivity of the forced swimming test.
The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment... more The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be p...
The authors evaluated respiratory response to cholecystokinin tetrapeptide (CCK-4) in healthy vol... more The authors evaluated respiratory response to cholecystokinin tetrapeptide (CCK-4) in healthy volunteers. Subjects were randomly assigned to either a CCK-4 (N = 15) or placebo (N = 15) challenge under double-blind conditions. Dyspnea was reported by all of the subjects who received CCK-4 but only one subject who received placebo. CCK-4 caused a significant increase in tidal volume and minute ventilation but had no effect on breathing frequency. Placebo had no effect on any of the respiratory measures. These data indicate that the behavioral effects of CCK-4 are accompanied by changes in respiration in healthy volunteers.
Cholecystokinin-tetrapeptide (CCK-4) and placebo were injected to 11 panic disorder patients. CCK... more Cholecystokinin-tetrapeptide (CCK-4) and placebo were injected to 11 panic disorder patients. CCK-4 induced a panic attack identical to spontaneous panic attacks in all patients; placebo did not induce any attacks. The role of CCK-4 in anxiety disorders is discussed.
Brofaromine is a new, reversible, and selective type-A monoamine oxidase inhibitor (MAOI) that al... more Brofaromine is a new, reversible, and selective type-A monoamine oxidase inhibitor (MAOI) that also has serotonin reuptake inhibitory properties. Its dual pharmacologic effects offer promise in the treatment of a wide spectrum of depressed patients while producing less severe anticholinergic side effects in comparison with standard drugs. A multicenter, double-blind, placebo-controlled study including 220 patients was undertaken to evaluate the efficacy and safety of brofaromine in major depression. This study of a fixed-dose design and 6 weeks' duration found that brofaromine was significantly better than placebo on the Overall Evaluation of Efficacy, Beck self-rating scale, HAM-D Bech subscale, HAM-D total 14 items (minus the three sleep items), HAM-D depressed mood item and retardation factor, and worse than placebo on the insomnia items of HAM-D. Significantly more patients on placebo than on brofaromine did not complete the trial due to lack of efficacy. In comparative cont...
Thirty-nine unipolar depressed patients were treated, after a washout period of seven days in a d... more Thirty-nine unipolar depressed patients were treated, after a washout period of seven days in a double blind study with either moclobemide, placebo or amitriptyline, for 42 days. The psychopathological assessment and HRSD were done on seven day intervals and thyroid analysis was done on 14 day intervals. At the end of therapy, the levels of T4 and fT4 decreased significantly in the responders if amitriptyline was used, and non-significantly if placebo or moclobemide were used. The T4 and fT4 values of the non-responders increased non-significantly. The weight change was minimal and non-significant.
Psychiatric journal of the University of Ottawa : Revue de psychiatrie de l'Université d'Ottawa, 1989
The author discusses adequate pharmacological treatment for depression. The discussion is based o... more The author discusses adequate pharmacological treatment for depression. The discussion is based on data from psychopharmacological research, from recommendations given in manuals of psychopharmacology, and from surveys of psychopharmacological practices of affective disorders clinics. The review is limited to the treatment of major depressive episodes with or without melancholia. The treatment of atypical and psychotic depressions is discussed elsewhere. The review is also limited to treatment with non-monoamine oxidase inhibitors antidepressants. The paper is divided in three parts: optimization of treatment; remission rates achieved by optimization of treatment; and lack of optimization of treatment in every day practice and research.
Benzodiazepines slow down the workings of the brain and the central nervous system. They are used... more Benzodiazepines slow down the workings of the brain and the central nervous system. They are used medically to reduce anxiety, to help people sleep and to relax the body. They should only be prescribed for short periods of time. This is because it is possible to become dependent on them after as little as four weeks’ use as directed by a doctor (see ‘Tolerance and dependence’ on page 2 in this fact sheet).
The acoustic startle reflex is a sensitive index of “anxiety” and “fear.” Potentiation of startle... more The acoustic startle reflex is a sensitive index of “anxiety” and “fear.” Potentiation of startle by conditioned and unconditioned fear stimuli appears to be mediated by the amygdala. CholecystokininB(CCKB) agonists increase “anxiety” in laboratory animals and induce “panic” in humans. Here, we investigate the role CCKBreceptor-mediated mechanisms in the amygdala in the potentiation of startle. First, intra-amygdala infusions of the CCKBreceptor agonist pentagastrin (0, 0.01, 0.1, 1, and 10 nm) produced a dose-related potentiation of acoustic startle responses. At the highest dose, startle amplitudes were increased up to 90% above preinfusion baseline levels. Second, similar infusions of pentagastrin had no effect on locomotor activity over the same time course, showing that increases in startle responsivity after infusions of pentagastrin are not attributable to nonspecific changes in motor activity. Third, infusions of similar doses of pentagastrin into the striatum or nucleus acc...
La cholecystokinine (CCK) a d'abord ete identifiee comme etant un peptide du systeme gastro-i... more La cholecystokinine (CCK) a d'abord ete identifiee comme etant un peptide du systeme gastro-intestinal avant qu'il ne soit mis en evidence au niveau du cortex cerebral. Son activite s'exprime grâce a deux types de recepteurs CCK A et CCK B . Des etudes chez l'homme ont montre que l'injection du tetrapeptide, la CCK 4 , induisait des attaques de panique aussi bien chez des volontaires sains que chez des patients presentant un trouble panique. Ces derniers se montrant plus sensibles que les volontaires sains a l'injection de CCK 4 CCK 4 s'avere donc un agent inducteur des attaques de panique au meme titre que le CO 2 ou le lactate. Du fait de sa presence physiologique dans le cerveau humain la question est posee de connaitre le role de la CCK dans la neurobiologie de l'anxiete.
The forced swimming test (FST) in mice has failed to predict antidepressant activity for drugs ha... more The forced swimming test (FST) in mice has failed to predict antidepressant activity for drugs having beta adrenoreceptor agonist activity and for serotonin uptake inhibitors. We investigated the potential for clonidine to render the FST sensitive to antidepressants by using a behaviorally inactive dose of this agent (0.1 mg/kg). All antidepressants studied (tricyclics, 5-HT uptake inhibitors, iprindole, mianserin, viloxazine, trazodone) showed either activity at lower doses or activity at previously inactive doses. The effect appeared specific because it did not appear with drugs other than antidepressants (diazepam, chlorpromazine, sulpiride, atropine), except for amphetamine and apomorphine which have a strong effect on the dopaminergic system. The use of behaviorally subactive doses of clonidine may thus provide an important means of increasing the sensitivity of the forced swimming test.
The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment... more The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be p...
The authors evaluated respiratory response to cholecystokinin tetrapeptide (CCK-4) in healthy vol... more The authors evaluated respiratory response to cholecystokinin tetrapeptide (CCK-4) in healthy volunteers. Subjects were randomly assigned to either a CCK-4 (N = 15) or placebo (N = 15) challenge under double-blind conditions. Dyspnea was reported by all of the subjects who received CCK-4 but only one subject who received placebo. CCK-4 caused a significant increase in tidal volume and minute ventilation but had no effect on breathing frequency. Placebo had no effect on any of the respiratory measures. These data indicate that the behavioral effects of CCK-4 are accompanied by changes in respiration in healthy volunteers.
Cholecystokinin-tetrapeptide (CCK-4) and placebo were injected to 11 panic disorder patients. CCK... more Cholecystokinin-tetrapeptide (CCK-4) and placebo were injected to 11 panic disorder patients. CCK-4 induced a panic attack identical to spontaneous panic attacks in all patients; placebo did not induce any attacks. The role of CCK-4 in anxiety disorders is discussed.
Brofaromine is a new, reversible, and selective type-A monoamine oxidase inhibitor (MAOI) that al... more Brofaromine is a new, reversible, and selective type-A monoamine oxidase inhibitor (MAOI) that also has serotonin reuptake inhibitory properties. Its dual pharmacologic effects offer promise in the treatment of a wide spectrum of depressed patients while producing less severe anticholinergic side effects in comparison with standard drugs. A multicenter, double-blind, placebo-controlled study including 220 patients was undertaken to evaluate the efficacy and safety of brofaromine in major depression. This study of a fixed-dose design and 6 weeks' duration found that brofaromine was significantly better than placebo on the Overall Evaluation of Efficacy, Beck self-rating scale, HAM-D Bech subscale, HAM-D total 14 items (minus the three sleep items), HAM-D depressed mood item and retardation factor, and worse than placebo on the insomnia items of HAM-D. Significantly more patients on placebo than on brofaromine did not complete the trial due to lack of efficacy. In comparative cont...
Thirty-nine unipolar depressed patients were treated, after a washout period of seven days in a d... more Thirty-nine unipolar depressed patients were treated, after a washout period of seven days in a double blind study with either moclobemide, placebo or amitriptyline, for 42 days. The psychopathological assessment and HRSD were done on seven day intervals and thyroid analysis was done on 14 day intervals. At the end of therapy, the levels of T4 and fT4 decreased significantly in the responders if amitriptyline was used, and non-significantly if placebo or moclobemide were used. The T4 and fT4 values of the non-responders increased non-significantly. The weight change was minimal and non-significant.
Psychiatric journal of the University of Ottawa : Revue de psychiatrie de l'Université d'Ottawa, 1989
The author discusses adequate pharmacological treatment for depression. The discussion is based o... more The author discusses adequate pharmacological treatment for depression. The discussion is based on data from psychopharmacological research, from recommendations given in manuals of psychopharmacology, and from surveys of psychopharmacological practices of affective disorders clinics. The review is limited to the treatment of major depressive episodes with or without melancholia. The treatment of atypical and psychotic depressions is discussed elsewhere. The review is also limited to treatment with non-monoamine oxidase inhibitors antidepressants. The paper is divided in three parts: optimization of treatment; remission rates achieved by optimization of treatment; and lack of optimization of treatment in every day practice and research.
Benzodiazepines slow down the workings of the brain and the central nervous system. They are used... more Benzodiazepines slow down the workings of the brain and the central nervous system. They are used medically to reduce anxiety, to help people sleep and to relax the body. They should only be prescribed for short periods of time. This is because it is possible to become dependent on them after as little as four weeks’ use as directed by a doctor (see ‘Tolerance and dependence’ on page 2 in this fact sheet).
The acoustic startle reflex is a sensitive index of “anxiety” and “fear.” Potentiation of startle... more The acoustic startle reflex is a sensitive index of “anxiety” and “fear.” Potentiation of startle by conditioned and unconditioned fear stimuli appears to be mediated by the amygdala. CholecystokininB(CCKB) agonists increase “anxiety” in laboratory animals and induce “panic” in humans. Here, we investigate the role CCKBreceptor-mediated mechanisms in the amygdala in the potentiation of startle. First, intra-amygdala infusions of the CCKBreceptor agonist pentagastrin (0, 0.01, 0.1, 1, and 10 nm) produced a dose-related potentiation of acoustic startle responses. At the highest dose, startle amplitudes were increased up to 90% above preinfusion baseline levels. Second, similar infusions of pentagastrin had no effect on locomotor activity over the same time course, showing that increases in startle responsivity after infusions of pentagastrin are not attributable to nonspecific changes in motor activity. Third, infusions of similar doses of pentagastrin into the striatum or nucleus acc...
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