摘要:

AbstractThe antidepressant efficacy of some of the newer 5‐HT uptake inhibitors is reviewed on the basis of the available data. The placebo controlled evidence of efficacy of the 5‐HT uptake inhibitors as a class is substantial with a broad range of antidepressant action and apparent equivalent efficacy to reference tricyclic antidepressants. Some selective advantage in treating anxiety or suicidal thoughts associated with depression is noted and the growing evidence of a unique selective role in treating obsessive compulsive disorder with or without depression is commented

ISSN:0885-6222    

DOI:10.1002/hup.470060502

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe serotonergic probe clomipramine (CMI) was used to measure the degree of activity of the serotonin system in pathological gamblers versus matched controls. To this end, intravenous CMI (12·5 mg) was given and prolactin (Prl), growth hormone (GH) and cortisol (C) levels were measured. Compared to controls, pathological gamblers show a blunted prolactin response, but no effects on GH and C levels. It is concluded that the 5‐HT system shows hypoactivity in pathological gamblers, and this finding supports the inclusion of pathological gamblers in the group of behavioural disturbances characterized by poor impulse contr

ISSN:0885-6222    

DOI:10.1002/hup.470060503

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

Abstract5‐HT uptake inhibitors have a definite place in the treatment of mood disorders, although their primary target is uncertain. Mood‐, anxiety‐, and aggression‐regulation are the most likely candidates. 5‐HT uptake inhibitors are also effective in Panic Disorder and OCD, where the primary target in PD is probably anxiety and in OCD either anxiety or aggression. It is recommended that 5‐HT uptake blockers should be studied in aggression disorders.Furthermore, it is concluded that the range of indications of selective 5‐HT uptake blockers can better be described dimensionally than nosologically, leading to a new era of clinical psychopharmacology, described as functional psych

ISSN:0885-6222    

DOI:10.1002/hup.470060504

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractEthanol interferes with several brain functions, namely with specific neurotransmission processes. Depletion of brain 5‐hydroxytryptamine (5‐HT) impairs the acquisition of tolerance to ethanol or facilitates its loss, while activation of 5‐HT brain transmission facilitates tolerance development and decreases ethanol consumption. One hypothesis which has been put towards is that genetically determined low 5‐HT brain levels may be related to a predisposition to alcoholism. Acute ethanol intake transiently increases brain 5‐HT turnover; therefore, ethanol consumption might be hypothesized as an attempt to correct a deficit of 5‐HT brain transmission. The findings that administration of selective 5‐HT neuronal uptake blockers (zimelidine, citalopram, fluvoxamine and fluoxetine) decrease ethanol intake has given further support to this hypothesis. However, the time course of this effect is different from the antidepressant action described for these compounds. Also, there is evidence to suggest that lower doses of the 5‐HT uptake blockers are needed in order to reduce ethanol intake in alcoholic patients; this, however, requires further investigation. Interestingly, other clinical entities which have been found to be associated with a hypothetical dysfunction in 5‐HT brain transmission, such as obsessive compulsive disorder, panic disorder and some forms of depression, have also been associated with alcoholism, and seem to respond as well to 5‐HT neuro

ISSN:0885-6222    

DOI:10.1002/hup.470060505

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThis chapter reviews and discusses the evidence supporting the role of 5‐HT in the mechanism of action of antidepressants in panic disorder (PD). The data were interpreted as compelling evidence in favour of a specific pharmacological effect on symptoms of panic and phobic avoidance. Results from our group provide strong circumstantial evidence as to the role of 5‐HT in these effects. In the light of the available data we have advanced the hypothesis that this effect of antidepressants might be mediated through stimulation of the postsynaptic, probably inhibitory, elements of the 5‐HT receptor in the septohippocampal area of the brain. Finally, the proposed mechanism of action does not preclude the involvement of other neuronal systems in certain dimensions of the psychopathology

ISSN:0885-6222    

DOI:10.1002/hup.470060506

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThis paper reviews the available data on the relationships between serotonin, impulsivity and suicide. It is concluded that low CSF‐5‐HIAA levels in psychiatric patients (depression, personality disorder, schizophrenia) and possibly also in supposedly healthy persons, increases the risk of suicide considerably. Other biological risk factors, e.g. activation of the hypothalamic—pituitary axis (positive dexamethasone‐suppression test) may also play a role. This trait marker is found in different kinds of impulsive behaviours: suicide, arson, murder, alcoholism, disinhibitory personality traits and others, indicating a marker of vulnerability, especially in crisis situations. Low output or low stability of the 5‐HT system in the CNS seems to increase im

ISSN:0885-6222    

DOI:10.1002/hup.470060507

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThis review concerns the pharmacology of the serotonergic systems in the CNS. After the description of the anatomy of the serotonergic system the synthesis, release and inactivation of the neurotransmitter 5‐HT is delineated. From the different serotonergic receptors (5‐HT1A, 5‐HT1B, 5‐HT1C, 5‐HT1D, 5‐HT2and 5‐HT3) the current status with regard to available ligands, second messenger systems and physiological roles has been outlined. The last part of the review extends the relationship between the 5‐HT and other neurotransmitter systems in the CNS (e.g. dopamine, noradrenaline, substance P, glutamate, acetylcholine a

ISSN:0885-6222    

DOI:10.1002/hup.470060508

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractReceptor binding studies revealed that flesinoxan potently and selectively binds to the 5‐HT1Areceptor (Ki= 1.7 nM). The anatomical distribution of [3H]‐flesinoxan binding sites is very similar to the localization of the 5‐HT1Asites labelled by [3H]‐8‐OH‐DPAT. In several functional models flesinoxan acted as a 5‐HT1Aagonist.Flesinoxan has been investigated in a variety of animal models predictive for anxiolytic activity. In a conflict test in pigeons, flesinoxan has potent anxiolytic activity at low doses (0.03–1 mg/kg i.m.). Flesinoxan is also highly active to reduce separation‐induced ultrasonic anxiety calls in infant rats and in an anticipatory anxiety model in adult mice. However, in the four‐plate test and the light‐dark model in mice, flesinoxan and other 5‐HT1Aagonists had no anxiolytic effects.Antidepressant properties of flesinoxan were shown in a behavioural despair model in rats: the forced‐swim test. Flesinoxan was more active (0.2–1.8 mg/kg s.c.) than classical tricyclic antidepressants. The putative antidepressant properties are also supported by the desensitisation of β‐adrenergic receptors in rats after subchronic administration of flesinoxan. In a functional test for β‐receptor activity in the brain (noradrenaline induced c‐AMP production in brain slices), a reduction of responsivity was observed after 2 weeks of treatment with flesinoxan (6 mg/kg/day).Therefore, based on the animal pharmacology there are strong indications that flesinoxan as a selective 5‐HT1Aagonist, has anxiolytic as wel

ISSN:0885-6222    

DOI:10.1002/hup.470060509

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractChlorimipramine, fluvoxamine and fluoxetine are clinically effective in obsessive‐compulsive disorder (OCD) and inhibit serotonin (5‐HT) reuptake. There are as yet no validated animal models for OCD. Therefore evidence for clinical efficacy in this illness has to be deduced from various preclinical tests. Different animal models for ‘anxiety’ clearly differentiate between the serotonin uptake inhibitors and the classical anxiolytics such as the benzodiazepines, drugs not very effective in the treatment of OCD. One animal ‘anxiety’ paradigm, ultrasonic distress calls in rat pups, appears as an attractive model to differentiate various anxiolytic agents and should be considered as a tool to detect putative anti‐OCD properties of drugs. The neurochemical profile of the selective 5‐HT uptake inhibitors such as fluvoxamine and fluoxetine obviously leaves very little room for alternative mechanistic hypotheses about the mechanism of action of their clinical efficacy, not only in OCD, but also in depression. It is speculated whether certain receptor types, notably 5‐HT1Creceptors, are particularly involved in the

ISSN:0885-6222    

DOI:10.1002/hup.470060510

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe present contribution describes the effects of 5‐HT1A, 5‐HT1B, 5‐HT1C, 5‐HT1D, 5‐HT2and 5‐HT3ligands in preclinical models of anxiety and aggression in rodents. 5‐HT1Aagonists show up as strong anxiolytic drugs in some animal paradigms, but not in all, and their behavioural profile is clearly different from that of benzodiazepines. 5‐HT1B,1C,1Dligands have mixed effects in anxiety paradigms; anxiolytic as well as anxiogenic responses have been observed, and some compounds were devoid of activity. The 5‐HT2ligands have no clear‐cut anxiolytic effects either, whereas 5‐HT3antagonists seem to exert anxiolytic effects, at least in some animal anxiety models. In offensive aggression, 5‐HT1Aagonists are not specifically anti‐aggressive, presumably due to sedation and interference with serotonergic behaviour. Mixed 5‐HT1A,1Bagonists appear specific antiaggressive agents, reducing offence without sedative or other unwanted side‐effects. Extensive studies have indicated that the 5‐HT1Bor some combination of 5‐HT1A/1Breceptors specifically modulates this anti‐offence effect (serenic‐profile). Neither 5‐HT1C, 5‐HT2nor 5‐HT3receptor ligands appear to have antiaggressive effects. These preclinical data await human studies in order

ISSN:0885-6222    

DOI:10.1002/hup.470060511

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY