Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endorphin neuropeptides may have neuroleptic-like effects on dopamine function and may be antischizophrenic. Ten chronic psychotic patients with neuroleptic-induced tardive dyskinesia and parkinsonism received placebo and des-tyrosine-gamma-endorphin (DT gamma E). Drug effects on movement disorders and eye-blinking rates were assessed by blind evaluations of randomly sequenced videotapes made during standardized examinations before and 30, 60, and 120 minutes after each injection and at 24 hours postinjection on days of consecutive treatment. Changes in schizophrenic symptoms were evaluated openly with the schizophrenia subscale of the Comprehensive Psychiatric Rating Scale. There were no significant effects of DT gamma E on any parameter and no side effects. This suggests that DT gamma E, within the tested dose range, does not influence the pathophysiology of neuroleptic-induced dyskinesias or chronic schizophrenia or have neuroleptic properties. However, DT gamma E is well tolerated and should be tested with higher doses during prolonged treatment.
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PMID:Effect of des-tyrosine-gamma-endorphin in tardive dyskinesia. 701 Dec 48

The effects of dopamine-antagonistic neuroleptic (NL) medication on saccadic eye movements were compared in matched groups of 40 NL-treated and 18 NL-free schizophrenic patients and in 18 NL-treated and 14 NL-free bipolar affective patients. Manipulation of the saccadic paradigm yielded data on four types of saccade: those reflexively elicited by novel stimuli (REFLEX saccades), those directed towards the remembered location of a target now extinguished (REM) or towards the location where a predictably alternating target is expected to appear (PRED), or ANTI saccades, directed away from the stimulus to the mirror image location. Extensive psychiatric, neurological and neuropsychological assessments were also carried out on all subjects. The saccades of NL-treated patients, regardless of diagnosis, were less spatially accurate than those of NL-free patients, with a greater tendency to fall short of the target when generated towards the locus of a mentally represented target. This effect was greatest with a predictably alternating target, especially during periods when target visibility was withdrawn, only a temporal cue remaining. This pattern of impairment which is also found in early stages of Parkinson's disease is likely to be due to deficiency of striatal dopamine. Its best clinical predictors were disease duration, and Webster-Parkinsonism scores. Failure to suppress reflexive saccades to the stimulus in the REM and ANTI paradigms were more closely associated with schizophrenia than with NL treatment and were best predicted by negative symptoms and Wisconsin perseverative errors, both of which are widely regarded as indicators of frontal lobe dysfunction.
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PMID:Saccadic abnormalities in psychotic patients. II. The role of neuroleptic treatment. 748 Apr 28

Phase II clinical trials with risperidone have proven it to have a potent antipsychotic effect, improving both positive and negative symptoms of schizophrenia. It was found to have a low potential for inducing extrapyramidal symptoms and has been shown to have a possible antidyskinetic effect without increasing parkinsonism. Risperidone has a rapid onset of action and a favourable side-effect profile. One-year data on risperidone suggest that its therapeutic action in patients with chronic schizophrenia can be maintained without the significant neurological side-effects associated with the use of standard neuroleptics.
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PMID:Clinical review of risperidone. 750 74

Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0-6; baseline: 42.0 +/- 2.3; mean +/- SEM), SAPS (64.5 +/- 4.8) and SANS (55.0 +/- 4.3) showed a moderate decrease at the end of treatment (BPRS: 30.0 +/- 3.5; SAPS: 36.1 +/- 6.7; SANS: 42.5 +/- 5.9), when intention-to-treat analysis was applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Seroquel (ICI 204 636), a putative "atypical" antipsychotic, in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters. 765 71

Recent research in computational neuroscience has suggested that psychosis associated with disturbed catecholamine neurotransmission may result from disturbances in the gain parameters of neural networks that these same secondary neurotransmitters are thought to control. We propose a mathematical model based upon cooperativity theory used in thermodynamics to explain how the gain parameter that momentarily increases the effect upon the post-synaptic cell of a given weighted connection from the presynaptic cell could be instantiated in the fluctuating electrical conductance of the dendrite of a neuron without requiring extensive ion transport or utilization of the ATP energy cycle. More specifically we propose that catecholamine neurotransmission serves to maintain the dendrite in a cooperative state with regard to changes in electrical conductance due to impulse traffic alone. In this way we supply the neuron with an activity driven gain parameter that not only increases volume of neuronal output at very low energy cost but that also upscales cooperative effects at the mechanico-chemical level of the dendrite to the network level itself. An important implication of this model is that two extreme states for dendritic electrical conductance will occur if cooperativity is lost at the level of catecholamine depletion or excess due to drug effects. These are the AND gate effect in which dendritic conductance is so low that the neuron requires extensive synaptic activity in order to output significantly. We correlate this state with negative symptoms in schizophrenia and psychomotor retardation in depression as well as the rigidity in Parkinsonism. The other extreme is represented by the OR gated dendrite in which conductance is so high that even noisy input to the dendrite will lead to significant nerve cell output. We correlate this condition with the positive symptoms of schizophrenia, the agitated features of psychotic depression and the tremors of Parkinsonism.
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PMID:A theory of cooperativity modulation in neural networks as an important parameter of CNS catecholamine function and induction of psychopathology. 787 Feb 71

Since the introduction of chlorpromazine in the 1950s, neuroleptic medications have been the mainstay of treatment of schizophrenia and other psychotic disorders. These medications do not always lead to complete remission of symptoms but they have allowed many patients to lead more productive and satisfying lives away from the restrictions of chronic hospitalisation. However, neuroleptics are associated with a number of adverse effects that can compromise their effectiveness. Extrapyramidal adverse effects include acute dystonic reactions, neuroleptic-induced Parkinsonism and akathisia. They can often be treated with neuroleptic dose reduction, addition of anticholinergic or beta-blocking agents, or medication change. Later-onset movement disorders such as tardive dyskinesia or dystonia require careful evaluation and may be treated with dose reduction or change of neuroleptic to an atypical agent. Potentially fatal reactions such as agranulocytosis and neuroleptic malignant syndrome can rarely occur and often require significant medical intervention. Clozapine offers some advantages over 'typical' neuroleptics but has a unique adverse effect profile which includes agranulocytosis.
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PMID:Adverse effects of antipsychotic drugs. 790 81

The presence of movement disorders was ascertained blind to treatment status in 35 schizophrenic patients. All were on neuroleptics and receiving, or had received earlier during the index episode, adjunctive bilateral electroconvulsive therapy (ECT). None manifested signs of neuroleptic-induced parkinsonism (rigidity, bradykinesia, or abnormal gait). Fine tremor of the hands was noted in two patients, and only one met criteria for probable mild tardive dyskinesia. The implications of these findings for understanding neurological complications associated with schizophrenia and its treatment with ECT are discussed. The hypothesis is proposed that ECT protects against neuroleptic-induced parkinsonism and thereby may reduce the risk for the subsequent development of tardive dyskinesia.
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PMID:Absence of neuroleptic-induced parkinsonism in psychotic patients receiving adjunctive electroconvulsive therapy. 791 62

The importance of persistent negative symptoms in schizophrenia as a limiting factor in psychosocial and vocational rehabilitation has been increasingly emphasized. As a result, treatment trials and new drug development programs are focusing more attention on negative symptoms. Unfortunately, there is enormous phenomenological overlap between negative symptoms and neuroleptic-induced parkinsonism. We report data from a cohort of 56 clozapine-treated patients demonstrating significant correlations between measures of akinesia and anergia. Despite an average drug washout of over 2 weeks, the persistence of drug-induced parkinsonism can confound the assessment of therapeutic drug effects on negative symptoms.
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PMID:Clozapine, negative symptoms, and extrapyramidal side effects. 796 79

Epidemiological studies suggest an apparent protective effect of cigarette smoking on the risk of Parkinson's disease. There is also a report suggesting that patients with Parkinson's disease who smoke are less likely to develop dementia. I investigated the relationship of smoking to the severity of cognitive functions and presence of drug-induced parkinsonism in a group of 111 neuroleptic-treated chronic institutionalized schizophrenic patients. Patients who smoked had significantly less cognitive impairment (p < .02) and a lower prevalence of drug-induced Parkinsonism (p < .02) compared to nonsmokers. These findings suggest that cigarette smoking may protect against the development of dementia and drug-induced Parkinsonism in schizophrenia.
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PMID:Cigarette smoking: effects on cognitive functions and drug-induced parkinsonism in chronic schizophrenia. 806 38

Schizophrenia and Parkinson's disease have been considered inversely related neuropsychiatric disorders since the former has been attributed to increased dopaminergic transmission while the latter is thought to result from loss of dopaminergic neurons. It is in line with this concept that the classical neuroleptic (anti-schizophrenic) drugs cause as a side effect a drug-induced type of Parkinsonism. Most etiopathogenetic models hold that the "neuroleptic malignant syndrome" may result from "over-therapy" of schizophrenia, causing too widespread a block of dopaminergic transmission. The same clinical condition can be triggered by rapid discontinuation of dopaminergic medication in Parkinson's disease. Further, neuroleptic malignant syndrome shares key clinical features such as extrapyramidal motor disturbances and hyperthermia with a severe form of clinical deterioration in Parkinson's disease patients, the akinetic Parkinsonian crisis. Both conditions, neuroleptic malignant syndrome and Parkinsonian crisis, are resistant to anticholinergic treatment but may well respond to drugs with N-methyl-D-aspartate (NMDA) antagonistic properties such as amantadine and memantine. We advocate the use of NMDA receptor antagonists in these medical emergencies and link their clinical efficacy to the common pathophysiological pathway of increased excitatory amino acid neurotransmitter activity in neuroleptic malignant syndrome, Parkinsonian crisis, and dopamine agonist withdrawal states.
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PMID:Glutamate receptor antagonists for neuroleptic malignant syndrome and akinetic hyperthermic parkinsonian crisis. 810 99


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