ISSN:0885-6222    

DOI:10.1002/hup.470020102

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractTranquillizers, and specifically benzodiazepines (BZD), have become one of the most widely used group of drugs in the world; some have suggested too widely used. Interest in these drugs is still extremely high, both from the scientific and sociological point of view. This is best documented by the fact that the present review is based on more than 700 articles published between 1981 and 1984 covering various aspects of clinical pharmacology.Pharmacokinetic studiesdealing with absorption, metabolism and elimination after acute and chronic administration demonstrate that the onset and duration of action of BZD after single oral doses depend largely on absorption rate and the rate and extent of distribution. The rate and extent of accumulation during multiple dosage depend on the elimination half‐life and clearance. A framework is proposed for classification of BZD according to the elimination half‐life. Various factors — such as age, sex, disease state and drug interaction — influence the pharmacokinetic properties of BZD.Pharmacodynamic studiesare mostly concerned with effects of the drug on the central nervous system (CNS), as well as on behaviour and neuroendocrine functions. The former include computer‐assisted quantitative analyses of the scalp‐recorded wake electroencephalogram (EEG), based on which it seems possible to determine if, how, when and at what dose a newly developed compound affects the human brain. Sleep investigations are now concerned not only with the effect of the drug on the all‐night sleep, but also on the quality of awakening and early morning behaviour as well as with residual effects during daytime, affecting mnestic and cognitive functions, psychomotor performance (specifically in regard to driving ability), as well as mood and affectivity. Finally, for almost a decade increasing concern has been expressed about the widespread use of tranquillizers in society. Scientific evidence concerning this issue will be reviewed so that an appropriate medical decision may be reached for the treatment of the individual patients after consideration of the beneficial effects as well as undesirable

ISSN:0885-6222    

DOI:10.1002/hup.470020103

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractLittle is known of the processes which confer vulnerability to the emergence of involuntary movements (tardive dyskinesia) in only a proportion of patients receiving long‐term treatment with neuroleptic drugs. There is no consistent evidence that patients with involuntary movements have received either longer or more vigorous pharmacotherapy, and it has proved difficult to demonstrate any general relationship between increasing neuroleptic exposure and the emergence of the syndrome. Advancing age may be associated more with deleterious changes in the central nervous system within individual patients that can raise vulnerability to the emergence of involuntary movements, than with particular predisposing patterns of neuroleptic exposure. The literature in schizophrenic patients reveals that two indirect and putative indices of ‘organicity’, namely cognitive dysfunction and negative schizophrenic symptoms, together with several CT indices of structural brain pathology, show similar and robust associations with the presence of involuntary movements. In schizophrenia, predisposition to the emergence of involuntary movements during long‐term neuroleptic therapy appears intimately related with particular features of the illness, especially those associated with clinical deterioration. It is argued from clinical and animal studies that neuroleptics may hasten the appearance of dyskinetic movements in individuals with the greatest likelihood of ultimately having such movements spontaneously as cerebral deterioration p

ISSN:0885-6222    

DOI:10.1002/hup.470020104

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe stereoenantiomers of piquindone (Ro 22–1319), a new antipsychotic pyrroloisoquinoline derivative, were labelled with the positron‐emitting isotope11C. Only the (−)‐enantiomer inherits most of the biological activity of racemic piquindone. The compounds were examined by positron emission tomography (PET) for dopamine‐D2 receptor binding in the living brain of Cynomolgus monkeys and healthy human subjects. After i.v. administration of tracer doses the (−)‐enantiomer but not the (+)‐enantiomer was shown to accumulate markedly in the dopamine‐D2 receptor rich caudate/putamen in both species. After (−)11C piquindone injection, radioactivity in the human caudate/putamen, and the putamen/cerebellar activity ratio increased to about 2 during the hour when radioactivity could be followed. (−)11C piquindone binding in the monkey putamen was not easily displaceable by haloperidol. The results demonstrate that (−) but not (+)‐11C piquindone has a high affinity for dopamine‐D2 receptors in the living human brain. The results are compatible with the view that clinical administration of piquindone produces a long‐lasting effect on central dopamine‐D2 receptors. (−)11C Piquindone is a useful ligand for visualization of dopamine‐D2 receptor binding by PET and for analysing relationships between antipsychotic effects of piquindone and blockade of specific binding sites in

ISSN:0885-6222    

DOI:10.1002/hup.470020105

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThirty‐four endogenously depressed outpatients were treated with desipramine following dexamethasone suppression tests (DSTs). When mean change scores on the Hamilton scale were compared between DST‐suppressors and non‐suppressors there was a clear trend toward more favourable response in the non‐suppressors. However, this finding fell just short of reaching statistical significance. Ten out of 13 DST‐non‐suppressors (77 per cent) responded to desipramine, while 10 out of 21 suppressors (48 per cent) responded. This difference was not

ISSN:0885-6222    

DOI:10.1002/hup.470020106

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe effects of nocturnal temazepam elixir on 14 male osteoarthritic patients and 16 age‐ and sex‐matched healthy controls were investigated in a double‐blind parallel groups study. Temazepam produced a number of significant changes in objective sleep. In the osteoarthritic patients temazepam reduced the duration of awakenings, percentage stage 0, percentage stage 1, percentage stages (0+1) and increased percentage stage 2 and REM latency. In the controls temazepam reduced the duration of awakenings, percentage stage 0, percentage stages (0+1) and increased percentage stage 2, sleep efficiency and REM latency. During the drug period, seven out of 15 subjects receiving temazepam reported improved sleep, compared with one out of 15 placebo subjects. There was no evidence to suggest that temazepam caused any unwanted side‐effects or affected the duration of morning stiffness in osteoarthritic patients. Temazepam produced no significant impairment of early morning psychomotor performance or significant withdrawal effects in either patients or c

ISSN:0885-6222    

DOI:10.1002/hup.470020107

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractA case of abuse of triazolam, a short‐acting benzodiazepine, was experienced. A 35‐year‐old male, with a tendency to mixed drug dependence with nitrazepam, etc., and a background of neurotic anxiety and insomnia, started self‐administration of triazolam. Application of triazolam was frequent, with large doses up to a maximum of 80 mg/day (320 times the recommended daily dose of 250 micrograms). In addition to psychic dependence, occurrence of withdrawal symptoms confirmed formation of physical dependence, which was also supported by EEG together with the appearance of various autonomic and psychic symptoms.Even though triazolam is known to be comparatively safe, this case confirms that it can induce physical dependence upon frequent administration of a large amount, together with psychic dependence, and therefore care must be taken with regard to dosage. In particular, self‐administration of the drug should be strictly c

ISSN:0885-6222    

DOI:10.1002/hup.470020108

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

ISSN:0885-6222    

DOI:10.1002/hup.470020110

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

ISSN:0885-6222    

DOI:10.1002/hup.470020112

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

ISSN:0885-6222    

DOI:10.1002/hup.470020113

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY