摘要:

Summary:Functional brain imaging with positron emission tomography (PET) has opened up new avenues for the investigation of possible functional disturbances related to psychiatric disease as well as pharmacodynamic assessment of drug treatment in vivo. Different strategies to study pharmacologic effects on the brain have been developed in recent years. The basic methods are to measure (a) blood flow or glucose metabolism, (b) parameters of specific receptor binding, or (c) neurotransmitter metabolism. Each of these can be performed either in a resting state or after perturbation with a pharmacologic challenge. Our group has developed a general strategy for investigating pharmacologic effects on brain function: (a) determining indirect drug‐induced metabolic changes with fluorodeoxyglucose PET and (b) characterizing functional interactions of neurotransmitter systems by assaying drug‐induced displacement of specific receptor ligands. These study designs reflect a paradigm shift where functional coupling of brain regions and interaction of different neurotransmitter systems are seen as the basis for a multitransmitter hypothesis of schizophrenia. In this view, any disturbance in the self‐regulatory process is reflected in the loss of functional interaction between systems. An overview of recent studies and their possible clinical importance will be presented.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:We explored the prevalence of respiratory dyskinesia (RD), diagnosed objectively using a spirograph, and the major risk factors for tardive dyskinesia (TD) and RD. A total of 258 inpatients treated with neuroleptics was interviewed, and TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). Movement of the chest and respiratory regularity were assessed on clinical examination. Spirographs of patients with suspected RD were recorded, and RD was diagnosed based on spirographic data and the concurrence of two investigators. The prevalence of TD in this study was 22.1% (57 of 258). Aging and organic brain damage (OBD) were confirmed as risk factors; female gender, mood disorders, and the duration of neuroleptic exposure were not. Ten of 28 patients suspected of having RD were diagnosed with RD on the basis of persistent respiratory irregularities without other physiologic causes. The overall prevalence of RD was 3.9% (10 of 258) and was 17.5% (10 of 57) among the TD patient population. Four of these patients complained of dyspnea, and three demonstrated grunting. RD was more highly associated with aging and OBD than with TD itself. The identification of risk factors for RD is not only helpful in planning prophylactic strategies, but also facilitates the understanding of the pathogenesis of this syndrome.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The objectives of this study were to assess potential pharmacokinetic and pharmacodynamic interactions between moclobemide and selegiline. Two groups of 12 healthy male and female subjects were treated with 200 mg moclobemide or 5 mg selegiline b.i.d. for 16 days. On study day 8, the alternative active drug or placebo was added to the respective treatments. Concentration‐time profiles of moclobemide and two of its main metabolites and 3,4‐dihydroxyphenylglycol (DHPG, a norepinephrine metabolite), 5‐hydroxy‐indoleacetic acid (HIAA, a serotonin metabolite), and 3,4‐dihydroxy‐phenylacetic acid (DOPAC, a dopamine metabolite) in plasma as well as MAO‐B activity and serotonin concentration in platelets were determined at steady state during monotreatment and combined treatment. The pharmacokinetic parameters of moclobemide and its metabolites changed on multiple dosing but were not influenced to a relevant extent by concomitant administration of selegiline. The measured pharmacodynamic parameters, expressed as the maximum effect on a study day and the area under the effect‐time curve, characterized the drugs' influence on peripheral neurotransmitter metabolism. The most reliable variables to assess inhibition of MAO‐A and ‐B in humans proved to be DHPG in plasma and serotonin in platelets and MAO‐B activity in platelets, respectively. Several variables (DHPG, platelet serotonin) suggested that selegiline has some MAO‐A inhibitory activity. This became particularly apparent upon addition of selegiline to moclobemide treatment; i.e., the effects of combined moclobemide and selegiline treatment were statistically greater than those of moclobemide monotreatment. Moclobemide alone exerted a slight inhibition of platelet MAO‐B activity. The reported pharmacodynamic interactions are not considered to be clinically relevant. However, due to the previously found supraadditive tyramine potentiation upon simultaneous treatment, moclobemide and selegiline should only be combined when applying dietary restrictions with respect to tyramine.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Concentrations ofpros‐methylimidazoleacetic acid (p‐MIAA) were measured in cerebrospinal fluid of 30 patients with chronic schizophrenia. Levels of p‐MIAA correlated negatively with mean scores of the Psychiatric Symptom Assessment Scale for positive symptoms (r= −0.48), but not negative symptoms, and with ventricular brain ratios (r= −0.48). Patients with abnormal ventricular enlargements had much lower concentrations of p‐MIAA than those with normal ventricles. These results suggest that processes that reduce accumulation of p‐MIAA in CSF may be associated with increased severity of symptoms among patients with chronic schizophrenia.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The present study investigates dopaminergic sensitivity in Parkinson's disease (PD) through the measurement of neuroendocrine (growth hormone: GH, prolactin: PRL) and cardiovascular (blood pressure: BP, heart rate: HR) responses to low doses of apomorphine (5 &mgr;g/kg s.c.) in three groups of subjects: 13 normal volunteers (controls), 19 “de novo” never‐treated PD patients, and 14 levodopa‐treated PD patients. Apomorphine did not change BP and HR but significantly decreased PRL plasma levels in controls as well as in the two groups of PD patients. GH plasma levels significantly increased after apomorphine. There was no significant difference in the changes in neuroendocrine (GH, PRL) parameters in the two groups of PD patients in comparison with controls. However, “de novo” patients exhibited a significantly higher number of apomorphine‐induced orthostatic symptoms (7 of 19) than did controls (0 of 13) or treated PD patients (2 of 14). These results show that hypothalamic dopaminergic sensitivity (studied through GH and PRL responses to apomorphine) is normal in PD. In contrast, because apomorphineinduced orthostatic hypotension is mainly due to the stimulation of peripheral dopaminergic receptors, our study suggests a peripheral dopaminergic hypersensitivity in some “de novo” never treated (but not in treated) PD patients.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:This is the first report on the evaluation of treatment with fasudil hydrochloride, a novel intracellular calcium antagonist, for wandering symptoms in patients with cerebrovascular dementia by using31P‐magnetic resonance spectroscopy (MRS) and Xe‐computed tomography (CT). The subjects studied were two patients with cerebrovascular dementia who had had frequent wandering episodes. The clinical diagnosis was Binswanger‐type cerebral infarction in patient 1 and sequelae of cerebral bleeding and multiple lacunar infarctions in patient 2. Treatment with fasudil at 30 or 60 mg/day was given orally for 8 weeks. The wandering symptoms disappeared in both patients during the treatment and reappeared a few days after discontinuation of the treatment. Mental tests indicated that memory was mildly improved during the treatment. Pretreatment31P‐MRS findings revealed decreases in relative signal intensities of phosphomonoester and phosphodiesters and an increase in that of mean adenosine triphosphates. After treatment, these findings disappeared. The regional cerebral blood flow values by Xe‐CT in both patients did not show significant changes from before treatment to the values after treatment. These results suggest that the efficacy of fasudil for the wandering symptoms and mental function observed in our patients may have been related to a direct effect on intracellular energy metabolism.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Acute single‐dose response of drug‐induced parkinsonism (DIP) to L‐Dopa and apomorphine challenge was evaluated in a double‐blind crossover study in 12 schizophrenic patients. There were two noteworthy negative findings. First, neither L‐Dopa nor apomorphine produced significant improvements in DIP and second, no changes (neither improvement nor worsening) were found in patients' psychiatric status. Findings suggest that, for a stimulation dose reaching almost 90% of the responsive dose for idiopathic Parkinson's disease, no significant changes may reasonably be expected in the parkinsonism of schizophrenic patients treated with neuroleptic drugs.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:This preliminary investigation examined the therapeutic efficacy of two doses of oral D‐cycloserine (5 and 15 mg p.o. b.i.d.) administered as an adjuvant to molindone (150 mg p.o. q.d.) in the treatment of schizophrenia. D‐Cycloserine is an agonist at theN‐methyl‐D‐aspartate (NMDA) subclass of glutamate receptor complex. An NMDA agonist intervention was studied because of the schizophreniform psychosis precipitated by phencyclidine (PCP), which is a noncompetitive antagonist at the NMDA glutamate receptor. The PCP model of schizophrenia is regarded as the most comprehensive pharmacological model of this disorder. In this preliminary, placebo‐controlled, double‐blind, parallel‐group study, the measures of treatment efficacy were the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms, and Clinical Global Impression Scale. The final scores for each item of the outcome measures employed were based on the consensus of at least two trained raters who were present during each rating interview. In the 13 subjects evaluated, although the D‐cycloserine was well tolerated, neither dose seemed to possess adjuvant therapeutic efficacy. However, since another recent report of nine patients with schizophrenia treated for 2 weeks with a slightly higher dose of D‐cycloserine (50 mg/day) described significant clinical and neuropsychological improvement, further study of the adjuvant potential of slightly higher doses of D‐cycloserine seems warranted. Additionally, there might be a therapeutic window for D‐cycloserine dosing, as daily doses of 250 mg have been associated with symptom worsening.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Enadoline, a selective agonist of the &kgr;‐opioid receptor, was studied for its analgesic efficacy in patients with pain after obstetric or gynecologic surgery. An initial study involving a comparison of enadoline (2, 5, 15&mgr;g), an acetaminophen‐codeine (ACET/COD) combination, and placebo showed all treatments to be ineffective analgesics. Therefore, a second study with the same design but using higher doses of enadoline (15 and 25&mgr;g) and replacing ACET/COD with morphine 10 mg i.m. was conducted. Enadoline 25&mgr;g produced similar pain relief to that of morphine, although of shorter duration, and better than enadoline 15&mgr;g or placebo. However, enadoline was associated with dose‐limiting neuropsychiatric adverse events, which led to early termination of the study.

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1996

数据来源: OVID