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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antipsychotic drugs, while ameliorating symptoms in schizophrenia, evoke extrapyramidal effects which resemble parkinsonism. We studied the potential of 1- (4,4-bis(4-fluorophenyl)butyl)-4-(4-fluorophenoxy)-1,2,3,6-tetrahydropyr idine d-tartrate to induce extrapyramidal side effects in Rhesus monkeys. This agent shares neurochemical effects of known antipsychotic agents in its ability to antagonize cerebral dopamine action by competing for (3H)-Haloperidol binding of the dopamine receptors and inhibiting limbic and striatal adenylate cyclase in rat brain. The compound was administered orally to monkeys for 18 days, starting at 2 mg/kg and increasing to 20 mg/kg. Additional groups of monkeys received the drug for 29 consecutive days at 5 and 7.5 mg/kg/day. In both studies, extrapyramidal signs were associated with neuropathological changes in the brains of treated monkeys. The findings resemble those reported in Rhesus monkeys and in drug addicts after repeated intravenous administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The findings also suggest a structure/activity relationship of tetrahydropyridine analogs with neurologic and associated neuropathologic manifestations produced in monkeys. The experimental model is useful to study the pathogenesis and possibly therapeutic approaches for Parkinson's disease.
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PMID:Parkinson-like syndrome in nonhuman primates receiving a tetrahydropyridine derivative. 348 56

Psychiatric disorders are common in medical inpatient and outpatient populations. As a result, internists commonly are the first to see psychiatric emergencies. As with all medical problems, a good history, including a collateral history from relatives and friends, physical and mental status examination, and appropriate laboratory tests help establish a preliminary diagnosis and treatment plan. Patients with suicidal ideation usually have multiple stressors in the environment and/or a psychiatric disorder (i.e., a major affective disorder, dysthymic disorder, anxiety or panic disorder, psychotic disorder, alcohol or drug abuse, a personality disorder, and/or an adjustment disorder). Of all patients who commit suicide, 70% have a major depressive disorder, schizophrenia, psychotic organic mental disorder, alcoholism, drug abuse, and borderline personality disorder. Patients who are at great risk have minimal supports, a history of previous suicide attempts, a plan with high lethality, hopelessness, psychosis, paranoia, and/or command self-destructive hallucinations. Treatment is directed toward placing the patient in a protected environment and providing psychotropic medication and/or psychotherapy for the underlying psychiatric problem. Other psychiatric emergencies include psychotic and violent patients. Psychotic disorders fall into two categories etiologically: those that have an identifiable organic factor causing the psychosis and those that have an underlying psychiatric disorder. Initially, it is essential to rule out organic pathology that is life-threatening or could cause irreversible brain damage. After such organic causes are ruled out, neuroleptic medication is indicated. If the patient is not agitated or combative, he or she may be placed on oral divided doses of neuroleptics in the antipsychotic range. Patients who are agitated or psychotic need rapid tranquilization with an intramuscular neuroleptic every half hour to 1 hour until the agitation and combativeness are under control. Haloperidol (Haldol) is the safest neuroleptic. Chlorpromazine (Thorazine), perphenazine (Trilafon), and, in the elderly, thiothixene (Navane) can also be useful if haloperidol (Haldol) is not effective and more sedation is needed; these drugs, however, produce more side effects. Violent patients need to be physically restrained and then given antipsychotic medication or, in the case of drug abuse or alcohol withdrawal, the appropriate drug management.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Psychiatric emergencies. 373 71

Haloperidol-induced increases in the number of dopamine receptors, as measured by [3H]spiperone binding to striatal membranes, do not occur in rats repeatedly treated with insulin in doses eliciting pronounced hypoglycemia. Given alone, however, insulin has no effect on [3H]spiperone binding in normal rats. These findings demonstrate a modulating effect of insulin on brain dopamine receptor sensitization. This effect might be relevant to the mechanism of insulin coma therapy in schizophrenia and is consistent with and supports the dopaminergic hypothesis of this disorder.
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PMID:Modulation of dopamine receptor supersensitivity by chronic insulin: implication in schizophrenia. 389 77

Auditory cortical evoked potentials of 20 schizophrenic patients with an acute exacerbation of the illness were investigated before neuroleptic medication and after remission of the acute symptoms, and compared with healthy controls matched for sex and age. Additionally, tests were conducted in 40 healthy volunteers to ascertain whether psychoticism or other personality factors were correlated with evoked potentials. The aim of the study was to test the overarousal hypothesis of schizophrenia and to control the effects of clinical state, neuroleptic medication and personality factors. Acutely ill schizophrenic patients had a shorter evoked potential N1 latency (Table 1). After remission of the symptoms under haloperidol N1 latency of the patients was no longer different from that of the controls. Patients after remission and on medication, however, had longer P2 and N2 latencies and a greater P2-N2 amplitude (Table 2). Psychoticism and extraversion were correlated negatively with amplitude data of components N1 and P2 in healthy volunteers. The results favor the overarousal hypothesis of schizophrenia. Haloperidol normalizes N1 latency in acutely ill patients. It's effect on later components of the evoked potentials seems comparable to a reduction in vigilance. Auditory evoked potentials might allow to follow up the effect of neuroleptics in acute schizophrenia. It seems necessary to consider personality factors when comparing patients with healthy controls in evoked potential studies.
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PMID:Schizophrenia, psychoticism, neuroleptics, and auditory evoked potentials. 404 64

In recent years, the complex treatment of schizophrenia has been extended by the neuroleptic large-dose therapy. Our investigations carried out so far, which reflect the experiences gained in several years with this form of treatment, include 30 schizophrenic patients admitted in an acute psychotic condition. They were treated for six days running with 40 to 120 (average 65) mg of Haloperidol daily. The results of our studies show that the large-dose therapy with Haloperidol as an initial phase of a combined pharmaco-therapy represents a safe, rapid and effective method.
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PMID:[Neuroleptic large dose therapy of schizophrenias]. 611 6

In addition to the dopamine hypothesis, a glutamate hypothesis has been recently discussed in the biochemical theories on the cause of schizophrenia. In schizophrenic patients less glutamic acid has been found in the cerebrospinal fluid. Glutamate is probably the most important excitatory transmitter of the mammalian forebrain. The liberation of glutamic acid in the striatum is inhibited by dopamine, more specifically by the D2 receptor, which is also though to be responsible for the antipsychotic effects of neuroleptic drugs. It seems possible that schizophrenia may be primarily caused by underfunction of glutamatergic corticostriatal and corticomesolimbic neurons rather than by overfunction of the dopaminergic system. The negative cognitive symptoms associated with schizophrenia would fit in with this hypothesis. The classical and the new atypical neuroleptic drugs show differential effects on glutamate and GABA in the brain tissue of the striatum and in the cerebrospinal fluid. Whereas sulpiride diminishes glutamate in the striatum and enhances glutamate in the cerebrospinal fluid, tiapride does not affect either of them. Correspondingly, tiapride does not show any antipsychotic effects. Haloperidol, on the other hand, enhances the GABA level in the striatum in a dose-related manner. These findings may perhaps prompt experimental research to find antipsychotic drugs with fewer side effects.
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PMID:[A biochemical theory of schizophrenia]. 615 Nov 20

In an open study, 18 patients suffering from an acute episode of schizophrenia and 18 patients with severe mania were given haloperidol at different dosage levels. Haloperidol plasma concentrations were measured and the status of the patients was evaluated at intervals using the Brief Psychiatric Rating Scale (BPRS). No correlation was found between the oral dose and the plasma concentrations in the schizophrenic group, but there was a low correlation for manic patients. In both groups, however, there was a correlation between these two parameters when the drug was given intramuscularly. There was no correlation between haloperidol plasma concentrations and the BPRS scores. Of the 36 patients 28 responded well to the treatment and were discharged from hospital. A good relationship between the clinical status as observed by the clinicians and the BPRS score was found. Plasma haloperidol concentration measurement was found to be a useful tool for the detection of non-compliance or excessive plasma levels. Accordingly, the present study indicates the value of drug level monitoring as a means to improve therapy.
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PMID:Plasma haloperidol levels and therapeutic response in acute mania and schizophrenia. 648 92

Haloperidol is safe and effective in children for relieving psychotic symptoms associated with childhood autism, schizophrenia and mental retardation. It is the drug of choice for Tourette's syndrome, and may be useful in nonpsychotic hyperactive or aggressive children to control acute episodes, or when the stimulants normally useful in hyperactive children are ineffective. Such children taking haloperidol not only become calmer, but are often better able to respond to other modalities of therapy and to school instruction. Dosage, initially low, is increased gradually to minimize drowsiness and extrapyramidal symptoms, the most common side effects. Haloperidol in children is usually well-tolerated.
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PMID:Haloperidol -- its use in children. 693 55

In the present study, thirty schizophrenics who showed low blood pressure and low voltage fast EEG at the onset of the disease were selected from many schizophrenics. As a control group, 50 schizophrenics without any abnormal findings in blood pressure and EEG were examined. The experimental group showed a remarkable improvement after using Haloperidol and Ethylephedrine. From the above described findings, we want to emphasize on one group of schizophrenia which had low blood pressure and low voltage fast EEG, and we speculated that the symptoms of schizophrenia seem to have a close relation to the dysfunction of diencephalon and lower brain; this dysfunction might cause a disharmony between the function of neocortex and the lower brain.
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PMID:Clinical study on one group of schizophrenia. 739 Mar 29

Risperidone (Risperdal) is a novel antipsychotic drug, with beneficial effects on both positive and negative symptoms of schizophrenia, and with a low incidence of extrapyramidal side effects (EPS). These particular properties have been attributed to the predominant and very potent serotonin 5-HT2 receptor antagonism of the drug combined with less potent dopamine D2 antagonism. In order to provide data on the degree to which various central neurotransmitter receptors are occupied in vivo, we performed ex vivo receptor occupancy studies with risperidone in comparison with clozapine and haloperidol in rats and guinea pigs. Various types of receptors, to which the compounds were known to bind to in vitro, were investigated precisely using receptor autoradiography in sections of the same rat brain except for histamine H1 receptors that were measured in the guinea-pig cerebellum. Risperidone (2 h after s.c. treatment) occupied 5-HT2 receptors at very low doses (ED50 = 0.067 mg/kg). Nearly full occupancy (> 80%) was achieved before H1, D2, alpha 1 and alpha 2 receptors became occupied (ED50 = 0.45, 0.66, 0.75 and 3.7 mg/kg, respectively). Clozapine displayed occupancy of H1 and alpha 1 receptors at low doses (ED50 = 0.15 and 0.58 mg/kg, respectively) and of 5-HT2, 5-HT1C, D2, alpha 2, cholinergic muscarinic and 5-HT1A receptors at higher doses (ED50 = 1.3, 1.8, 9.0, 9.5, 11 and 15 mg/kg, respectively). Haloperidol occupied D2 and alpha 1 receptors at low doses (ED50 = 0.13 and 0.42 mg/kg, respectively) and 5-HT2 receptors at a higher dose (ED50 = 2.6 mg/kg). Occupancy of receptor types occurred with similar ED50-values in various brain areas, e.g. D2 receptors in striatum and mesolimbic areas. The ED50-values for the ex vivo measured occupancy of 5-HT2 and D2 receptors were in good agreement with ED50-values for functional effects putatively mediated by these central receptors. The dose-dependent occupancy of D2 receptors proceeded more gradually with risperidone (slope in the caudate-putamen: 0.85) than with clozapine (slope: 1.44) or haloperidol (slope: 1.51). It has previously been suggested that partial D2 receptor occupancy may suffice to control the positive symptoms of schizophrenia, whereas higher D2 receptor occupancy would induce extrapyramidal symptoms (EPS). The dose ratio for high (75%) vs. low (25%) D2 receptor occupancy in the caudate-putamen, was 37.3 for risperidone, 8.4 for clozapine, and 7.9 for haloperidol.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography. 751 May 74


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