Abstract:
:The therapeutic concentrations of antipsychotic drugs in the patient's plasma water or spinal fluid are identical to their blocking potencies in vitro at the dopamine D2 receptor, with the exception of clozapine which acts at D4. The variation in K values between laboratories stems from the fact that the apparent K value for any antipsychotic drug depends on the affinity of the competing radioligand for the receptor or the membranes. Clozapine at the D2 receptor has a K value of 420 nM using [3H]nemonapride, 180 nM using [3H]spiperone and 82 nM using [3H]raclopride. These K values are related to the tissue/buffer partition coefficients of the ligands. Extrapolating down to either 1 or 0 partition yields the intrinsic K values for the antipsychotic in the absence of any competing ligand. The extrapolated or intrinsic K value for clozapine at D4 is 1.3 nM, in agreement with the value of 1.1 nM measured directly with [3H]clozapine at D4. Clozapine in vivo, however, must compete with endogenous dopamine in the synapse, estimated as 50 nM. Thus, the in vivo concentration of clozapine for 75% occupation of dopamine D4 receptors can be derived as approximately 14 nM, in agreement with the observed value of 12-20 nM in the plasma water or spinal fluid in treated patients. In L-DOPA psychosis in Parkinson's disease, the clozapine concentration (in the plasma water or spinal fluid) for 75% blockade of dopamine D4 receptors may be predicted as approximately 3 nM, in general agreement with the value of approximately 1.2 nM in Parkinson patients who have L-DOPA psychosis. These considerations provide strong support for the conclusion that clozapine primarily targets the D4 receptor in psychosis. Using the same considerations for haloperidol, it can be shown that the haloperidol therapeutic concentration required for 75% blockade of dopamine D2 receptors in vivo will be approximately 2-3 nM, in agreement with the observed value in the spinal fluid or plasma water of 1-3 nM.
journal_name
Int Clin Psychopharmacoljournal_title
International clinical psychopharmacologyauthors
Seeman Psubject
Has Abstractpub_date
1995-09-01 00:00:00pages
5-13eissn
0268-1315issn
1473-5857journal_volume
10 Suppl 3pub_type
杂志文章,评审abstract::Lithium is widely used in the treatment of bipolar disorder. Here we describe the syndrome of irreversible lithium-effectuated neurotoxicity in a patient within therapeutic doses and levels, which persisted after discontinuation of Lithium. A 50-year-old gentleman with Bipolar disorder presented with symptoms of Mania...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/YIC.0000000000000341
更新日期:2021-03-01 00:00:00
abstract::The interaction between a single dose of 20 mg of prazepam and 0.5 g/kg body weight ethanol was investigated in 12 healthy male volunteers by nine objective performance tests, eight visual analogue self-rating scales and measurement of prazepam and ethanol plasma concentrations, using a double-blind three-way crossove...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004850-199100640-00004
更新日期:1991-01-01 00:00:00
abstract::Several cardiovascular risk factors have been linked to antipsychotic treatment and cardiovascular mortality is increased in these patients compared to the general population. The full metabolic syndrome (or its components) is associated with an increased risk of cardiovascular disorders. The prevalence of the metabol...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/01.yic.0000188215.84784.17
更新日期:2006-03-01 00:00:00
abstract::The clinical trial programme of sertraline, a selective serotonin re-uptake inhibitor, has shown the drug to have a favourable safety and toleration profile. In contrast, the tricyclic antidepressant, amitriptyline, produced a significant level of side effects, particularly anticholinergic. The side-effect profile of ...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章,评审
doi:10.1097/00004850-199112002-00007
更新日期:1991-12-01 00:00:00
abstract::Major depressive disorder (MDD) is currently the second most common cause of disability worldwide. Current treatment of MDD with selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors is limited by efficacy and tolerability issues, highlighting the unmet need in the treatment of patien...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章,评审
doi:10.1097/YIC.0b013e3282f2b3cb
更新日期:2008-03-01 00:00:00
abstract::C-reactive protein (CRP) is an inflammatory marker associated with obesity, insulin resistance, and cardiovascular disease. A recent study found CRP levels to be higher in individuals treated with certain antipsychotic medications such as olanzapine; however, it is not clear whether this is associated directly with dr...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/YIC.0b013e3283400cd3
更新日期:2011-01-01 00:00:00
abstract::Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome, afflicting approximately 5% of all women of fertile age. The cardinal symptoms are irritability and anger. In addition, sadness, tension and carbohydrate craving are common complaints. The symptoms surface regularly between ovulation and menstruat...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1999-05-01 00:00:00
abstract::Most antidepressants in clinical use are believed to function by enhancing neurotransmission of serotonin [5-hydroxytryptamine (5-HT)] and/or norepinephrine (NE) via inhibition of neurotransmitter reuptake. Agents that affect reuptake of both 5-HT and NE (serotonin-norepinephrine reuptake inhibitors) have been postula...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章,评审
doi:10.1097/YIC.0b013e3282f41d7e
更新日期:2008-05-01 00:00:00
abstract::Social dysfunction is often associated with depressive disorders and its evaluation is an important measure of treatment outcome. The aim of this study was to assess the effect of two treatments, venlafaxine and amitriptyline, on the social functioning of depressed patients. Twenty-eight outpatients, meeting criteria ...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00004850-200207000-00003
更新日期:2002-07-01 00:00:00
abstract::The negative symptoms of schizophrenia remain a major clinical challenge. Reboxetine is an antidepressant whose major mechanism of action is as a noradrenergic reuptake inhibitor. This study was a 6-week randomized placebo-controlled trial of reboxetine or placebo add on to haloperidol 5 mg in the treatment of 30 pati...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004850-200109000-00004
更新日期:2001-09-01 00:00:00
abstract::Although the effects of atypical antipsychotics with regard to improving neurocognitive function are not sufficiently high. The present study applied an atypical antipsychotic monotherapy for patients with acute schizophrenia to (1) examine the percentage of patients who respond well to this treatment, (2) explore the...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/YIC.0000000000000293
更新日期:2020-03-01 00:00:00
abstract::Out of ten consecutive patients with DSM-III-R obsessive-compulsive disorder without any previous history of bipolarity, three patients showed antidepressant-induced hypomania (clomipramine, one patient; fluvoxamine, two patients) within the first 5 to 8 weeks of the drug treatment. These data support the previous res...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/00004850-199609000-00008
更新日期:1996-09-01 00:00:00
abstract::Since the discovery that clomipramine was effective in the treatment of obsessive-compulsive disorder (OCD), trials of several different medications for OCD have been published. The question of which agent, if any, is the medication of choice in OCD is of real clinical concern. Published clinical trials were collected...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章,meta分析
doi:10.1097/00004850-199503000-00002
更新日期:1995-03-01 00:00:00
abstract::The aim of this study was to investigate the prevalence of benzodiazepine and related drug (BZDR) use, especially long-term use, and associated factors among community-dwelling individuals with and without Alzheimer's disease (AD). We utilized data from the MEDALZ-2005 cohort, which includes all community-dwelling ind...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/YIC.0000000000000080
更新日期:2015-07-01 00:00:00
abstract::The objective of the present study was to evaluate the efficacy of mianserin and trazodone as antidepressants with serotonin 2 antagonist properties on negative symptoms and tardive dyskinesia in elderly patients with chronic schizophrenia. In this double-blind, placebo-controlled study the dose of each drug was incre...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00004850-199707000-00003
更新日期:1997-07-01 00:00:00
abstract::Three placebo-controlled double-blind and crossover trials were carried out to analyze the effects of oral yohimbine (YOH) 0.8 mg/kg on mood and performance in 16 healthy students. Subjective assessments (visual analogue scales, side-effects on questionnaire) and objective measurements (digit symbols, flicker fusion, ...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004850-198807000-00003
更新日期:1988-07-01 00:00:00
abstract::Methylamphetamine given intravenously as a single 15 mg dose led to a pronounced elevation of mood in 7 out of 21 depressed patients compared to a control injection of sterile water administered on another occasion in random order under double-blind conditions. All 7 responders experienced an increase of VAS self-rati...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004850-198604000-00004
更新日期:1986-04-01 00:00:00
abstract::Stevens-Johnson syndrome is a severe and potentially life-threatening cutaneous reaction associated with lamotrigine. The incidence of developing Stevens-Johnson syndrome during lamotrigine therapy is low. On the basis of the glutamate and dopamine neuron dysregulation hypothesis in schizophrenia, we propose new strat...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/01.yic.0000224789.21406.81
更新日期:2007-07-01 00:00:00
abstract::Using spectral analysis of heart rate, several studies have shown that panic disorder patients are characterized by a reduced heart rate variability (HRV), indicative of abnormalities in autonomous nervous system (ANS) function. We recently reported that patients with panic disorder, who did not respond to pharmacothe...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00004850-200203000-00005
更新日期:2002-03-01 00:00:00
abstract::Post-traumatic stress disorder (PTSD) is frequently treated with antidepressant medications, especially the newer selective serotonergic antidepressants which have documented efficacy in PTSD. Analogous to depression, however, some PTSD patients may not have a satisfactory response to these agents. This case report de...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/00004850-199809000-00008
更新日期:1998-09-01 00:00:00
abstract::This analysis characterizes patients with schizophrenia or schizoaffective disorder treated with risperidone who met remission criteria. In a 50-week, open-label trial, stable patients received long-acting injectable risperidone every 2 weeks. Remission criteria included severity (absent-mild ratings on core symptoms ...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/01.yic.0000224791.06159.88
更新日期:2007-01-01 00:00:00
abstract::The objective of this paper was to assess the effects of switching from typical and/or atypical antipsychotics to ziprasidone, owing to inadequate response or intolerance, in chronic schizophrenic patients. A total of 312 patients were switched to an 8-week, open-label, flexible dose (40-160 mg/day) of ziprasidone. Ps...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/YIC.0b013e3282f94905
更新日期:2008-07-01 00:00:00
abstract::Panic disorder has recently been recognized as a distinct sub-type of anxiety which may occur with or without phobic avoidance. Controlled prospective trials have demonstrated the efficacy of the tricyclic antidepressants and monoamine oxidase inhibitors in the treatment of this disorder. The use of benzodiazepines an...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章,评审
doi:10.1097/00004850-198601000-00002
更新日期:1986-01-01 00:00:00
abstract::The 6-month prevalence of depression in the Italian community was evaluated by means of the modified-Mini-International-Neuropsychiatric Interview (MINI) administered with a computer-prompted interview to a representative panel of 3550 individuals. Major depression and minor depression accounted for 8.0% and 2.9% of t...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/00004850-200101000-00006
更新日期:2001-01-01 00:00:00
abstract::On the basis of numerous previous studies, the serotonergic system plays a role in the pathogenesis of obsessive-compulsive disorder (OCD) and effective agents in this pathway, such as 5-hydroxytryptophan, can potentially contribute to treatment of patients with this disorder. Evaluating the efficacy of 5-hydroxytrypt...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/YIC.0000000000000321
更新日期:2020-09-01 00:00:00
abstract::Arrhythmias are a frequent and potentially fatal side effect of antipsychotic treatment. Strict ECG monitoring and clinical interviews are the standards used to prevent arrhythmias. A biologic predictive tool is missing. The identification of a genetic makeup at risk of antipsychotic-induced arrhythmias is the aim of ...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/YIC.0000000000000198
更新日期:2018-01-01 00:00:00
abstract::Fifty-five patients with moderate to sever panic disorder were treated for 9 weeks with alprazolam or imipramine and were then, except for one patient who had committed suicide, re-examined after on average 3 years of treatment. At follow-up most patients (74%) did not suffer from panic attacks at all. In the beginnin...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004850-199300820-00006
更新日期:1993-07-01 00:00:00
abstract::Zopiclone, a cyclopyrrolone with hypnotic properties was compared with temazepam and placebo in the treatment of insomnia. After a week's washout period, suitable subjects were allocated at random to zopiclone 7.5 mg or temazepam 20 mg or placebo for 2 weeks. Measurements of psychomotor function using the Leed's psych...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004850-199007000-00001
更新日期:1990-07-01 00:00:00
abstract::The interactions between warfarin and antidepressants can have potentially serious consequences resulting from enhanced or reduced anticoagulant activity. Information about such interactions was obtained from a Medline and hand search of the published literature, and by directly contacting manufacturers. The different...
journal_title:International clinical psychopharmacology
pub_type: 杂志文章,评审
doi:10.1097/00004850-199803000-00006
更新日期:1998-03-01 00:00:00
abstract::Two selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, both at a daily dose of 20 mg, were compared in patients with unipolar major depression treated in general practice. This was a multicentre, double-blind, randomized trial carried out in France. The duration of treatment was 8 weeks. Patie...
journal_title:International clinical psychopharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1996-06-01 00:00:00