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1.
氯氮平、氟哌啶醇和氯丙嗪对慢性精神分裂症患者糖、脂代谢及体质量的影响 总被引:14,自引:0,他引:14
目的 探讨氯氮平、氟哌啶醇和氯丙嗪对慢性精神分裂症患者的糖、脂代谢和体质量的影响。方法 对服用氯氮平(89例,氯氮平组),服用氟哌啶醇(87例,氟哌啶醇组)及服用氯丙嗪(83例,氯丙嗪组)治疗的慢性精神分裂症患者于治疗前后的不同时间进行血糖、胰岛素、血脂及体质量测定,并做相关因素分析。结果 氯氮平组治疗第90天和第180天空腹血糖异常(空腹血浆血糖〉7.0mmo/L)的发生率分别为8%及24%,氟哌啶醇组分别为1%和2%,氯丙嗪组分别为1%及4%。治疗第90天氯氮平组和氯丙嗪组的空腹及餐后2h血糖浓度均较治疗前升高,治疗第180天的血糖浓度高于第90天,氟哌啶醇组各时点的变化则不明显;差异均有统计学意义(P均〈0.01)。治疗第90天,氯氮平组的体质量平均高于治疗前5.5%,氯丙嗪组高于治疗前4.8%;治疗第180天两组分别高于治疗前9.1%和7.4%;氟哌啶醇组则无明显变化;三组间的差异有统计学意义(P〈0.01)。三组患者治疗第180天的胰岛素浓度均高于治疗前,差异均有统计学意义(P均〈0.01),但三组间的差异无统计学意义(P〉0.05)。氯氮平组和氯丙嗪组的胆固醇和甘油三酯浓度均高于治疗前,差异均有统计学意义(P均〈0.01),氟哌啶醇组则无明显变化。治疗第180天氯氮平组和氯丙嗪组患者血糖、胰岛素、血脂浓度与体质量均有一定相关性(r=0.23-0.39);氯氮平组的血糖、体质量、血脂代谢还与血药浓度呈显著性相关(r=0.28-0.62),差异均有统计学意义(P〈0.05或〈0.01)。结论 氯氮平和氯丙嗪治疗影响慢性精神分裂症患者的糖、脂代谢及体质量。 相似文献
2.
目的 探索常敏和超敏状态时乙酰胆碱酯酶活性的变化及该变化与锥体外系症状(EPS)的可能关系。方法 应用分光光度法测定大鼠脑皮层、海马和纹状体AchE催化碘化乙酰硫代胆碱水解的速率而确定酶的活性。结果 急性给予利血平、氯氮平、氟哌啶醇对大鼠纹状体、海马和皮层的AchE活性无显著影响;以相同剂得的利血平、氯氮平和氟哌啶醇连续给药7d和21d,利血平和氟哌啶醇显著降低纹状体和海马AchE活性,氯氮平仅在 相似文献
3.
Effects of antipsychotic drugs on latent inhibition: sensitivity and specificity of an animal behavioral model of clinical drug action 总被引:1,自引:1,他引:0
Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.Preliminary data were presented in part at the Society for Neuroscience Annual Meeting, Phoenix, AZ, 1989 相似文献
4.
L. Farde F. -A. Wiesel P. Jansson G. Uppfeldt A. Wahlen G. Sedvall 《Psychopharmacology》1988,94(1):1-7
Raclopride, a highly selective D2-dopamine receptor antagonist, was administered in doses up to 4 mg b.i.d. to ten schizophrenic patients in an open label non-comparative study lasting 4 weeks. Safety, tolerability, potential antipsychotic effect, prolactin response and drug effect on plasma homovanillic acid were evaluated. Central D2-dopamine receptor occupancy was determined by positron emission tomography (PET). No major deviations were found in biochemical and physiological safety parameters. Raclopride was well tolerated. The mean BPRS score was reduced by 55% at endpoint. In the global evaluation seven patients were very much or much improved. Extrapyramidal side effects were recorded in four patients and disappeared after dose reduction or single doses of biperiden. An increase in plasma prolactin of short duration was observed in both sexes. A significant decrease of plasma HVA was obtained after 4 weeks of treatment. In two of the patients the central D2-dopamine receptors occupancy was measured using PET. The receptor occupancy was 68 and 72% which is the same as that found in patients treated with conventional neuroleptics. 相似文献
5.
Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol fluphenazine > loxapine > trifluoperazine > thiothixene > molindone > clopenthixol > chlorpromazine > metoclopramide > thioridazine > clozapine > sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre-frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose. 相似文献
6.
Müller MJ Gründer G Wetzel H Müller-Siecheneder F Marx-Dannigkeit P Benkert O 《Psychiatry research》1999,89(3):1309-280
Antipsychotic efficacy and side effects of the selective sigma ligand EMD 57445 (panamesine) were investigated in 12 patients (6 males, 6 females) who met DSM-III-R criteria for schizophrenia. A 4-week open clinical study revealed only modest effects of EMD 57445 and its metabolites on positive and negative symptoms of schizophrenia. Extrapyramidal and other side effects were moderate, although a significant increase in mild dyskinetic movements was found. Five patients, four of whom were females, completed the trial. Dropouts were mainly due to treatment failure. Antipsychotic effects were significantly greater in female than male patients. 相似文献
7.
The atypical antipsychotic olanzapine was compared to other atypical as well as typical antipsychotic agents for in vivo
occupancy of D1, D2, D3, 5HT2, and muscarinic receptors in rat brain. Blockade of D2 receptors was determined by measuring the levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). To assess
the interaction with phosphoinositide (PI)-coupled 5HT2A and muscarinic receptors in vivo, we used a novel radiometric technique to measure in vivo PI hydrolysis. The antagonism
of olanzapine and other antipsychotic agents on 5HT2A and muscarinic receptors was determined by in vivo blockade of PI hydrolysis, stimulated by the 5HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) or the muscarinic agonist pilocarpine. Olanzapine inhibited 5HT2, D2, and D3 in vivo binding with high potency (ID50 = 0.15, 0.6 and 1.2 mg/kg, IP, respectively), while inhibiting D1 and muscarinic in vivo binding with much less potency (ID50 > 10 mg/kg, IP). The binding of olanzapine to D2 receptors in neostriatum was well correlated with the increase of DOPAC (ED200 = 0.8 mg/kg, IP) in vivo, indicating dopamine D2 antagonism. In vivo PI hydrolysis was increased by DOI in frontal cortex and by pilocarpine in hippocampus up to 2- and 7-fold
above the basal level, respectively. The agonist-induced increases in PI hydrolysis were fully blocked by the 5HT2A antagonist MDL100907 and the muscarinic antagonist scopolamine, indicating the mediation by 5HT2A receptors in frontal cortex and PI-coupled muscarinic receptors (m1, m3, and m5) in hippocampus, respectively. Olanzapine
was about 8-fold more potent in vivo in blocking DOI-induced stimulation of PI hydrolysis (ID50 = 0.1 mg/kg, IP) than pilocarpine-induced stimulation of PI hydrolysis (ID50 = 0.8 mg/kg, IP). In conclusion, olanzapine is more potent in blocking the 5HT2A receptor than D1, D2, D3 and muscarinic receptors in vivo, consistent with its favorable clinical profiles. In addition, the novel in vivo PI hydrolysis
assay proved to be a useful and reliable in vivo method to assess the functional efficacy of compounds that interact with
the 5HT2 and muscarinic receptors.
Received: 10 February 1998/Final version: 22 April 1998 相似文献
8.
W. Timmerman M. Heijmen B. H. C. Westerink R. Bruggeman J. A. den Boer 《Psychopharmacology》1999,144(3):286-294
Rationale: Previously, we have shown that the atypical antipsychotics clozapine and risperidone, unlike haloperidol, decreased the
firing rate of substantia nigra reticulata (SNR) neurons. As the SNR receives substantial input from the striatum, an area
where motoric side-effects of antipsychotics are thought to be mediated, the SNR might be an interesting brain structure with
regard to motor side-effects. Objective: The newly developed atypical antipsychotic olanzapine was studied for its effects on the firing rate of SNR cells. In addition,
to gain insight in the implications of our experimental setup for clinical use, responses upon clozapine, olanzapine and haloperidol
were studied after chronic treatment. Methods: In chloralhydrate-anaesthetized male Wistar rats, extracellular recordings were made from SNR neurons upon intravenously
(IV) administered cumulative doses of the antipsychotics. Naive rats and rats that were subcutaneously (SC) injected for 21
days with an antipsychotic were used. Results: Olanzapine (50–1600 mg/kg; IV), significantly inhibited the firing rate of the SNR neurons. Upon 21 days of treatment with
a daily SC injection of 20 mg/kg clozapine, the challenge on day 22 with cumulative injections of clozapine (200–6400 mg/kg;
IV) significantly inhibited the firing rate of the SNR neurons. Olanzapine (50–1600 mg/kg; IV) also significantly inhibited
the SNR activity when pretreated with olanzapine in an SC administered dose of 1 mg/kg, but not 5 mg/kg. Haloperidol (12.5–800 μg/kg;
IV) did not significantly affect the SNR activity in rats pretreated with SC administered 0.5 mg/kg haloperidol. Conclusions: Upon acute and chronic administration of clozapine and olanzapine versus haloperidol, differential effects on SNR neuronal
firing could be obtained. The experimental setup seem to be valid for further studies into the mechanism of action of typical
versus (relatively low doses of) atypical antipsychotics. The implications of the inhibitory effect of atypical antipsychotics
on the SNR firing rate are presently unknown, but could be associated with the lower propensity to induced motoric side-effects.
On the other hand, the SNR activity might also reflect non-motoric activity possibly related to negative symptoms.
Received: 11 December 1998/Final version: 20 January 1999 相似文献
9.
B. M. Cohen D. J. Ennulat F. Centorrino S. Matthysse H. Konieczna H.-M. Chu S. Cherkerzian 《Psychopharmacology》1999,141(1):6-10
The dopamine D4 receptor may be a site through which the clinical effects of antipsychotic drugs are mediated. Polymorphisms of a 48 base
pair repeat in the third exon of the DRD4 gene code for different length segments in the third intracytoplasmic loop of the
D4 receptor. The most common long (seven repeat) form of the D4 receptor has been shown in both physiologic and pharmacologic experiments to respond differently to dopamine agonists and
antagonists than do shorter forms of D4. Thus, variants of D4 may partly determine patient response to antipsychotic drugs and, in particular, response to typical neuroleptics, which
have a relatively low affinity for the D4 receptor, as compared to clozapine, which has a relatively high affinity for D4. DRD4 polymorphisms in the third intron were characterized in 28 patients with chronic psychosis who responded well to typical
neuroleptics, 32 patients who responded well to clozapine, and 57 healthy comparison subjects. Patients responding to typical
neuroleptics carried the allele for the long (seven repeat) form of the D4 receptor (allele frequency 8.9%) less frequently than patients responding to clozapine (allele frequency 23.4%, P = 0.046) or healthy comparison subjects (allele frequency 26.3%, P = 0.004). The results of this study suggest that inherited variants of D4 may explain some of the interindividual variation seen in patient response to different classes of antipsychotic medication.
Received: 10 October 1997/Final version: 20 May 1998 相似文献
10.
Effects of antipsychotic drugs on cytokine networks 总被引:7,自引:0,他引:7
Pollmächer T Haack M Schuld A Kraus T Hinze-Selch D 《Journal of psychiatric research》2000,34(6):746-382
It has been known since the 1950s that phenothiazines have immunomodulatory effects. This review summarizes recent evidence suggesting that antipsychotic drugs, in particular chlorpromazine and the atypical compound clozapine, influence the production of cytokines. Cytokines, organized in networks of related peptides with pleiotropic functions, are pivotal humoral mediators of infection and inflammation, and they play an important role in hematopoiesis and autoimmunity. Therefore, the effects of antipsychotic drugs on cytokine networks are important for the understanding of immune-mediated side effects of these drugs, e.g. agranulocytosis. In addition, modulation of cytokine production by antipsychotic agents suggests that these drugs might be useful for the treatment of diseases which primarily involve the immune system. Moreover, because cytokines are known to have numerous effects on the CNS, they may mediate effects of antipsychotic drugs on brain functions. Finally, the influence of antipsychotic drugs on cytokine networks is an important confounding factor in studies investigating disease-related immunopathology in psychiatric disorders. This review provides a synopsis of the data published on these topics and outlines future research perspectives. 相似文献