PubMed Health⌕ Search

Biomedical subjects

J Bradwejn

Publications and source records attributed to J Bradwejn.

At least 19 recordsLinked to original sources
PubMed1992

A dose-ranging study of the behavioral and cardiovascular effects of CCK-tetrapeptide in panic disorder.

Recent animal studies have shown that pretreatment with centrally active cholecystokinin (CCK) antagonists blocks the anxiogenic effects of CCK-tetrapeptide (CCK-4). In order to determine whether pretreatment with these antagonists can block the anxiogenic effects of CCK-4 in patients with panic disorder, a suitable challenge dose of CCK-4 must be selected. Thus, we conducted a dose range study in which patients with panic disorder (n = 29) were challenged with CCK-4 (10, 15, 20, or 25 micrograms) or placebo on two separate occasions, in a balanced incomplete block design. Patients received in random order 10 micrograms (n = 12), 15 micrograms (n = 11), 20 micrograms (n = 12), or 25 micrograms (n = 12) of CCK-4 or placebo (n = 11). CCK-4 induced anxiety and panic responses in a dose-dependent fashion. The incidence of panic attacks following the CCK-4 challenge was 17% (10 micrograms), 64% (15 micrograms), 75% (20 micrograms), and 75% (25 micrograms). None of the patients panicked with placebo. Moreover, a strong linear relationship between CCK-4 and increases in heart rate and diastolic blood pressure was found. The findings of this study suggest that a dose of 20 micrograms of CCK-4 (ED75) might be suitable for efficacy studies of CCKB antagonists and other potential antipanic drugs in patients with panic disorder.

Adolescent↗
PubMed1992

A comparison of moclobemide, amitriptyline and placebo in depression: a Canadian multicentre study.

In a 7-week prospective multicentre study, the efficacy, tolerability and safety of moclobemide were compared to those of amitriptyline and placebo in parallel groups of out-patients (n = 173) fulfilling the DSM III-R criteria for a major depressive episode. Participants were required to have a minimum baseline total score of 18 on the 17-item Hamilton Depression Rating Scale (HAMD). After a 1-week placebo washout, patients were randomly allocated to the three treatment groups. Assessment of efficacy, as judged by the number of responders achieving a 50% reduction in HAMD score by the end of treatment, showed that both moclobemide and amitriptyline were significantly superior to placebo, but that they were not significantly different from each other. Both treatments differed significantly from placebo with respect to the Physician's Global Assessment of Efficacy ('very good' or 'good' response: moclobemide 57%, amitriptyline 60% and placebo 35%). Assessment of tolerance as judged by the spontaneous reporting of adverse events showed a significant superiority of moclobemide over amitriptyline, but there was no significant difference between moclobemide and placebo. At termination of the study, amitriptyline patients showed a significant elevation of heart rate both supine (10.8 beats/min) and standing (15.5 beats/min), as well as significant weight gain (1.7 kg), but no changes were seen in the moclobemide or placebo groups. In conclusion, both moclobemide and amitriptyline were found to be more effective than placebo in the treatment of depression, while moclobemide had fewer side effects.

Adult↗
PubMed1992

Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.

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 present in clinical treatment and warrant investigation in humans.

Alprazolam↗
PubMed1991

Enhanced sensitivity to cholecystokinin tetrapeptide in panic disorder. Clinical and behavioral findings.

We studied the action of cholecystokinin tetrapeptide (CCK-4) in patients with panic disorder and normal controls. Subjects received, in random order, one injection of CCK-4 and one injection of placebo (saline) on two separate days in a double-blind crossover design. Two doses of CCK-4, 50 and 25 micrograms, were administered to two different samples of subjects. The panic rate with 50 micrograms of CCK-4 was 100% (12/12) for patients and 47% (7/15) for controls. The panic rate with 25 micrograms of CCK-4 was 91% (10/11) for patients and 17% (2/12) for controls. Nine percent of patients compared with 0% of controls panicked with placebo. These findings concur with previous reports of a panicogenic effect of CCK-4 and suggest that patients with panic disorder are more sensitive to the panicogenic effect of the peptide than are normal controls.

Adult↗
PubMed1991

Behavioral models in mice. Implication of the alpha noradrenergic system.

1. The mechanism of action of drugs might change according to the test used. Several noradrenergic drugs were tested in order to understand their implication in the mobility tests. 2. It was found that clonidine, an Alpha 2 agonist, acted differently according to the test used. It provoked sedation in spontaneous activity test, and anti-immobility effects in the other tests. 3. Tail suspension test is able to show the double acting of clonidine. 4. Idazoxan might act either as an alpha 2 antagonist or as partial alpha 2 agonist. TST shown the unexpected partial alpha agonist effect of the molecule. 5. Forced swimming test is more specific for predicting antidepressant activity than tail suspension test which is close to a spontaneous activity model.

Adrenergic alpha-Antagonists↗
PubMed1991

Comparison of the panicogenic effect of cholecystokinin 30-33 and carbon dioxide in panic disorder.

1. Twenty-two patients who met DSM-III-R criteria for panic disorder received either cholecystokinin 30-33 (25 micrograms i.v.) or 33% carbon dioxide. 2. The principal outcome measures of the study included the number and sum intensity of panic symptoms and the incidence of panic attacks. 3. The incidence of panic attacks tended (P = .07) to be higher with cholecystokinin 30-33 than with carbon dioxide. Nevertheless, patients who panicked within each group did not differ significantly with regard to the number and sum intensity of symptoms or symptom profile. 4. That cholecystokinin 30-33 and 35% carbon dioxide induced panic attacks which were qualitatively and quantitatively similar suggest that these agents might act on distinct systems that have a final common target or a final common mechanism of action.

Adult↗
PubMed1991

Comparison of the effects of cholecystokinin-tetrapeptide and carbon dioxide in health volunteers.

Twenty-six healthy volunteers received either 25 micrograms of cholecystokinin-tetrapeptide (CCK-4) or a mixture of 35% carbon dioxide in oxygen (CO2). DSM-III-R criteria including anxiety, apprehension and/or fear of at least moderate intensity were used to determine the occurrence of a panic attack. Results for the entire sample revealed that CCK-4 produced significantly more intense symptoms than CO2, but not a significantly greater number of symptoms. The incidence of DSM-III-R panic attacks was similar with both substances; 21% (3/14) for CO2 and 17% (2/12) for CCK-4. This study indicates that CCK-4 is at least as potent as CO2 in producing panic symptoms in healthy volunteers and is a useful challenge paradigm for comparative research of pharmacologic agents which possess distinct neurobiologic properties.

Adult↗
PubMed1991

[Clinical and neurobiological aspects of long-term administration of psychotropic drugs].

In neuroleptic therapy for psychotic illnesses, clinical improvement occurs much later than central dopamine blockade, and its time course varies widely among patients. A hypothesis explaining neuroleptic-responsive illness cannot be explained by dopamine blockade alone. Nevertheless, experimental data suggest that this mechanism may be a step in the therapeutic process for schizophrenia. Explanations are suggested for the time lag in therapeutic response for neuroleptics, including the hypothesis of delayed inactivation of mid-brain dopamine neurones. Chronic benzodiazepine treatment elicits adaptive responses in the CNS that are manifested as functional tolerance and physical dependence. Possible mechanisms involved in such a profound alteration of neuronal functioning are suggested. Down regulation of benzodiazepine receptors has been shown to be related to functional tolerance under certain conditions. The effect of repeated treatment with antidepressants is compatible with the hypothesis that changes in central monoamine transmission are involved in the activity of these drugs. Beta-adrenergic receptors are desensitized and their density is decreased; alpha-2 adrenoreceptors sensitivity is reduced, and post-synaptic serotoninergic receptors sensitivity is increased. It remains to be clarified whether some of the changes have larger role than others or whether they all contribute to the psychotropic drug activity in the therapeutic process.

Anti-Anxiety Agents↗
PubMed1991

Clonidine as a sensitizing agent in the forced swimming test for revealing antidepressant activity.

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.

Animals↗
PubMed1991

Dose ranging study of the effects of cholecystokinin in healthy volunteers.

The authors determined whether response to cholecystokinin-tetrapeptide (CCK-4) was dose-dependent. Healthy volunteers (n = 36) received double-blind injections of either 9 micrograms, 25 micrograms, or 50 micrograms of CCK-4 and placebo in a randomized sequence of injection. Significant dose-related differences were found for the number of symptoms, sum intensity of symptoms and the time until onset of symptoms, but not for the duration of symptoms. The incidence of panic attacks with CCK-4 was 11%, 17% and 47% for the 9 micrograms, 25 micrograms and 50 micrograms dose, respectively. None of the controls panicked with placebo injections. These results support the notion of a dose-dependent effect of CCK-4-induced panic symptoms. Implications of these findings in the neurobiology of panic attacks are discussed.

Adult↗
PubMed1990

Double-blind comparison of the effects of clonazepam and lorazepam in acute mania.

A double-blind comparison of clonazepam and lorazepam was conducted in 24 patients with acute mania. Patients received either clonazepam or lorazepam alone for 14 days. Treatment with lorazepam produced marked improvement in symptomatology, while treatment with clonazepam failed to demonstrate a significant therapeutic effect. Sixty-one percent of patients responded to treatment with lorazepam, with 38.5% achieving remission. This compares to an 18.2% response rate and 0% remission rate in patients treated with clonazepam. These findings support the usefulness of lorazepam in the treatment of acute mania.

Acute Disease↗