Pharmacological comparison of antipsychotic drugs and sigma-antagonists in rodents.

We compared antipsychotic drugs (haloperidol, chlorpromazine and clozapine) and sigma antagonists (remoxipride, cinuperone, alpha-(4-fluorophenyl)-4-(-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY 14802) and rimcazole) in the radio-ligand binding and behavioural experiments in rodents. A good correlation was established between the affinity of compounds at dopamine2-receptors in the striatum and their ability to block apomorphine-, amphetamine- and quipazine-induced behavioural effects in rodents. By contrast, no correlation was found between the behavioural effects of these drugs and their affinity at dopamine1-5-HT2- and sigma receptors.

Evidence for potentiation by CCK antagonists of the effect of cholecystokinin octapeptide in the elevated plus-maze.

Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 micrograms/kg, s.c.

Additive effects of lithium and antidepressants in the forced swimming test: further evidence for involvement of the serotoninergic system.

In the mouse forced swimming test (FST) pretreatment with a subactive dose of lithium (1 mEq/kg), given IP 45 min before the test, facilitated the antidepressant activity of iprindole, fluoxetine, and moclobemide (given IP 30 min before the test). These antidepressants (ADS) were not active alone in the FST in this study. Moreover, when subactive lithium was combined with a wide range of ADS, each given at subactive doses, those ADS with serotoninergic properties (e.

Effects of flumazenil on cholecystokinin-tetrapeptide-induced panic symptoms in healthy volunteers.

The neuropeptide cholecystokinin-tetrapeptide (CCK-4) has potent anxiogenic action in human and animal subjects. On the basis of prior work which demonstrated that benzodiazepine (BZD) receptor agonists antagonized CCK-induced excitation of rat hippocampal neurons we studied whether BZD receptors mediated the anxiogenic effect of CCK-4. To examine this possibility we determined whether the BZD receptor antagonist flumazenil could antagonize the effects of CCK-4 (50 micrograms) in healthy volunteers.

[Iprindole: a functional link between serotonin and noradrenaline systems?].

Iprindole is an active antidepressant in clinical practice but its mechanism of action has never been clearly defined. Serotoninergic regulation of noradrenergic neurons of locus coeruleus depends on 5-HT2 receptors. This regulatory action of the 5-HT system appears to facilitate the down-regulation of beta receptors.

Subdiaphragmatic vagotomy does not prevent the anti-exploratory effect of caerulein in the elevated plus-maze.

We compared the action of subdiaphragmatic vagotomy upon the anti-exploratory and motor depressant effects of caerulein, an agonist of cholecystokinin (CCK) receptors, in male rats. Vagotomized rats entered more frequently into the open arms of elevated plus-maze compared to intact control rats. Caerulein (1 microgram/kg subcutaneously (s.

Effects of low doses of lorazepam on psychometric tests in healthy volunteers.

The effects of low oral doses of lorazepam on several cognitive and performance tasks were investigated in 50 healthy students. A double-blind, parallel group design was used to compare five treatments: placebo and lorazepam 0.5, 0.

Mesoglycan and sulodexide act as stabilizers and protectors of fibroblast growth factors (FGFs).

Heparin and heparan sulfate proteoglycans (HSPGs) stabilize FGFs which belong to heparin-binding growth factors (HBGFs) on active conformation. They also strongly potentiate their mitogenic activity on many cell types, and protect them against thermal denaturation and enzymatic degradation. In the present work we have tested two heparin-like substances named mesoglycan and sulodexide obtained from bovine intestinal mucosal extracts.

Has iprindole an alpha adrenergic activity?

1. Acute administration of iprindole potentiated the toxicity of 1-norepinephrine and increased the intensity of oxotremorine-induced tremors. 2.

Replication of action of cholecystokinin tetrapeptide in panic disorder: clinical and behavioral findings.

Eleven patients with panic disorder were challenged with cholecystokinin tetrapeptide (CCK-4) on two occasions. The effects of CCK-4 were consistent except symptom onset was more rapid with the second injection. Demonstrating that the effects of CCK-4 are reproducible in panic patients opens the doors for studies of the effects of drug treatment on CCK-4-induced panic.

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.

Effects of administration route on pharmacokinetics of viloxazine in the rabbit.

The absorption of viloxazine chlorhydrate was investigated in ten rabbits. Each animal received the drug (15 mg/kg) by three routes: intravenous, gastric and duodenal. Viloxazine plasma concentrations were low when administered by gastric and duodenal routes compared to those after intravenous injection.

The cholecystokinin hypothesis of panic and anxiety disorders: a review.

It has been suggested that cholecystokinin, a neurotransmitter found in high density in mammalian brain, might be implicated in the neurobiology of panic and anxiety disorders. Cholecystokinin-tetrapeptide induces panic attacks analogous to spontaneous panic attacks in patients suffering from panic disorder and to a much lesser degree in healthy volunteers, suggesting an enhanced sensitivity to cholecystokinin-tetrapeptide in panic disorder. In animal models of anxiety, pre-treatment with cholecystokinin antagonists significantly decreases the anxiogenic effects of cholecystokinin agonists.

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).

[Is cholecystokinin a biological support in panic attacks?].

Cholecystokinin (CCK) is a peptide found high density in the cerebral cortex, the amygdala and the hippocampus of the mammalian brain. Molecular forms of varying amino acid lengths of CCK have been isolated. The sulphated octapeptide (CCK-8S) is the most abundant form and shorter molecular forms are also present in the brain.

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.

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.