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)

Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors, e.g., limb flick and abortive groom, characteristic of the action of hallucinogenic drugs and dependent on a depression of central serotonergic neurotransmission. This drug treatment produced large decreases (-40 to -60%) in central nervous system serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), when measured either 6 or 24 hr after the last amphetamine injection. The rate of limb flicking returned to a predrug level approximately 5 days after drug withdrawal, at which time 5-HT and 5-HIAA levels had returned to within 30 to 40% of base line. Both 5-HT and 5-HIAA returned to base-line levels within 14 days after drug withdrawal. Norepinephrine (NE), dopamine (DA) and DA metabolites were decreased 60 to 95% by chronic amphetamine treatment and showed little recovery within the 14 days after drug withdrawal. A second experiment examined the latency to onset of the behavioral and neurochemical changes with a constant dose of amphetamine (7.5 mg/kg, twice daily). Limb flicking was significantly increased above base-line levels following 3 days of amphetamine administration, at which time 5-HT and 5-HIAA levels were decreased 30 to 40%. NE, DA and DA metabolites were decreased approximately 50 to 90% by this treatment regimen. A third experiment examined the effects of a low dose of amphetamine (3.75 mg/kg), injected more frequently (every 6 hr for 6 days), to approximate the administration pattern in human amphetamine abuse. This treatment produced significant increases in limb flicking and abortive grooming on days 5 and 6 and resulted in 30 to 40% depletions of 5-HT and 5-HIAA. NE, DA and DA metabolites were decreased by approximately 50 to 90%. These data are discussed in relation to a role for serotonin in amphetamine psychosis and schizophrenia.
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PMID:Chronic amphetamine administration to cats: behavioral and neurochemical evidence for decreased central serotonergic function. 50 68

Ondansetron hydrochloride dihydrate is a 5-hydroxytryptamine (5-HT3) antagonist that was recently approved by the Food and Drug Administration for the treatment of chemotherapy-induced emesis. The mechanism of action is thought to be due to competitive inhibition of specific serotonin receptors in the central nervous system and gastrointestinal tract. In clinical trials with cisplatin-induced emesis, ondansetron resulted in complete control of vomiting (0-2 episodes) in 55-87% of patients during the first 24 hours of chemotherapy administration. It was significantly more effective than metoclopramide in comparative trials. Ondansetron is also being investigated for the treatment of radiation- and anesthesia-associated nausea and vomiting. Studies in animals demonstrate potential efficacy in the treatment of anxiety, drug withdrawal, and schizophrenia. The drug is generally well tolerated, with no reported extrapyramidal reactions.
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PMID:Parenteral ondansetron for the treatment of chemotherapy- and radiation-induced nausea and vomiting. 153 80

Evidence is reviewed that 5-HT (5-hydroxytryptamine, serotonin) acting through the 5-HT3 receptor subtype can influence behaviour relevant to anxiety, schizophrenia and cognitive disorders, and that 5-HT3 receptor antagonists such as ondansetron (CAS 116002-70-1) can correct behavioural disturbance in the absence of effect on normal behaviour. The 5-HT3 receptor antagonists exert a breadth of action over a wide dose range in rodent and primate models to inhibit aversive behaviour in animal models of anxiety and certain symptoms of withdrawal from drugs of abuse, alcohol, nicotine, diazepam and cocaine, to antagonise increased locomotor activity caused by mesolimbic dopamine excess, and facilitate performance in cognitive tests. The studies reveal an important role for 5-HT3 receptors in the regulation of limbic-cortical functioning, and a critical role for 5-HT3 receptor antagonists to establish the role of 5-HT3 receptors in schizophrenia, anxiety, drug withdrawal phenomena and cognitive disturbance. Preliminary clinical trials indicate a positive effect of ondansetron in anxiety, schizophrenia, alcohol withdrawal and age associated memory impairment.
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PMID:Serotonin and psychiatric disorders. A key to new therapeutic approaches. 158 95

Despite the proven efficacy of neuroleptic drugs in the acute and maintenance pharmacotherapy of schizophrenia, practical methods for identifying patients who require neuroleptic treatment to prevent relapse are lacking. This study evaluated the use of a methylphenidate challenge test to predict the outcome in 34 stable outpatients with schizophrenia receiving neuroleptic treatment. Patients received two infusions, one of methylphenidate and one of placebo, in randomized order one week apart while receiving neuroleptic treatment and again three weeks after drug withdrawal. Behavioral, cardiovascular, and neurologic responses were evaluated before and after infusion under double-blind conditions. Patients were then followed up without medication for 52 weeks or until symptom recurrence. The results indicate that specific measures, including behavioral response to methylphenidate, presence of tardive dyskinesia, and, under specific pharmacologic conditions, tardive dyskinesia, blink-rate, and pulse-rate responses to methylphenidate, are associated with time and propensity to relapse following neuroleptic withdrawal. These measures may be potentially useful in the identification of candidates for neuroleptic withdrawal and/or dosage-reduction treatment strategies.
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PMID:Prediction of relapse in schizophrenia. 288 10

Thirty-two patients in remission were followed by regular ratings during a prospective neuroleptic withdrawal study. They were outpatients who fulfilled the DSM-III criteria of schizophrenia and who were motivated for drug withdrawal. The relapse rate was 81%. The results from the rating scales confirm the hypothesis that a symptom increase occurs before psychotic relapse. In the order statistical differences occurred, the factors predicting relapse were those concerned with positive psychopathology, motor dysfunction, impaired affects and sleep disturbances. The corresponding symptoms and signs were mainly concerned with thought disorders, paranoid ideation, overactivity, depression and insomnia middle, all of nonpsychotic degree of severity. If prodromes appear, the patient should resume his neuroleptic treatment, or other preventive measures should be taken. By such therapeutic interactions, psychotic relapse may be prevented, or can be dealt with in an outpatient setting.
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PMID:Schizophrenic relapse after drug withdrawal is predictable. 370 94

The effects of different intervening variables on dexamethasone suppression test (DST) results were evaluated in depressed, schizophrenic, and manic patients. There was a significant correlation between age and DST results in major depression. Some "isolated peaks" of DST nonsuppression were explained by low dexamethasone serum levels. In schizophrenic and manic patients, the dexamethasone concentrations increased to above the normal range during the study period. A significant negative correlation between dexamethasone concentrations and DST results was found in schizophrenia and mania, but not in depression. Dexamethasone levels were generally higher in men than in women. Weight loss and hospital admission affected the DST in individual cases, whereas length of episode and drug withdrawal did not. Thus, the intervening variables accounted for some of the abnormal DST results, but other factors such as severity of illness, nonspecific stress, or possibly depression itself emerged as the main causes of abnormal DST results.
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PMID:Serial dexamethasone suppression tests in psychiatric illness: Part III. The influence of intervening variables. 373 87

The need for long-term neuroleptic treatment in nuclear schizophrenia depends on several factors, including the type of chronic schizophrenia, the phase of the disease, and the patient's total social situation. A neuroleptic drug withdrawal study demonstrated a need for further neuroleptic treatment for survival in the community even when the most symptom-free and socially best adapted chronic schizophrenics were considered. Prevention of relapse can apparently be achieved with lower neuroleptic doses than those necessary for optimal symptom suppression. Moreover, the patient's evaluation of his total social situation, including some quality-of-life aspects, must be considered as well as measures to avoid the patient becoming a burden on his family and his friends. Neuroleptic treatment in adequate antipsychotic doses usually means a risk of early, immediate and possibly late side effects. In striking a balance between benefit and risk it seems preferable to keep the benefit strategy, which means that the main point will be to monitor neuroleptic and antiparkinsonian drugs with regard to optimal symptom suppression not accepting any possible late side effects as a guideline.
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PMID:The need for long-term neuroleptic treatment in schizophrenia. 611 33

We have conducted a 6-wk drug withdrawal study in a group of chronic schizophrenic outpatients who had been maintained on injectable fluphenazine decanoate for at least 2 yr prior to the study. After two baseline assessments, patients were randomly assigned to two groups. The first group (holiday) received a placebo injection from a nurse who was not involved in the assessment (N = 17). The second group continued on their regular medication (N = 14). The assessment was done in a double-blind fashion at 3 and 6 wk using the Schedule for Affective Disorders and Schizophrenia (SADS) and the Global Assessment Scale (GAS) inventories to assess symptom status. Tardive dyskinesia was measured using the Abnormal Involuntary Movement Scale (AIMS). Community adjustment was assessed by means of the self-rated Weissman Social Adjustment Scale. We found that there were no relapses of any kind in either group of patients using the instruments mentioned above. The prevalence of tardive dyskinesia as measured by the AIMS was low, with only one patient having severe tardive dyskinesia. There was no significant worsening of the tardive dyskinesia during the drug holiday. Our study concludes that a 6-wk drug holiday was safe in this group of chronic schizophrenic patients maintained on fluphenazine decanoate. In contrast to other studies, no cases of covert tardive dyskinesia were detected during the drug holiday.
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PMID:Effects of a six-week drug holiday on symptom status, relapse, and tardive dyskinesia in chronic schizophrenics. 611 84

These clinical data may offer some support for the hypothesis that opiates have antidepressant, antimanic, and antipanic effects. This hypothesis should be studied directly by double-blind studies of the effects of exogenous and synthetic endogenous opioid peptides in patients with major depressive illness, panic and anxiety states, schizophrenia, and schizo-affective illness. These clinical data support our studies in nonhuman primates and man which suggest a common LC or NE hyperactivity may underly both drug withdrawal and spontaneous panic states. Whether endorphin deficiency or derangements account for the postulated NE hyperactivity needs additional study and we will discuss our preliminary work later. Failure of endorphins to terminate bursts in LC firing rate and NE release may be responsible for both of these types of panic states. In addicts, this mechanism could exist prior to opiate use, or abuse of potent exogenous endorphinomentic compound may cause an endorphin-abnormality. Both of these possibilities would be compensated by continuous opiate maintenance. Methadone maintenance is a complicated psychiatric, psychological, and social phenomenon. Further studies are necessary to evaluate the role of opiate maintenance in treating or suppressing the emergence of underlying psychopathology. Previous psychiatric hospitalization or treatment for a schizophrenic or affective illness may contraindicate absolutely the use of clonidine or other rapid detoxification methods. These data suggest the possibility of substituting a nonaddicting psychotropic medication for opiates in some patients who are self-medicators. The clinical data support other data suggesting the potential antipsychotic, antidepressant, and antianxiety/antipanic effects of the endogenous opioids, endorphins, and exogenous opioids, endorphins, and exogenous opiates. These and other data suggest potential utility for opioid agonists and endorphin testing in psychiatric treatment and diagnosis.
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PMID:Antimanic, antidepressant, and antipanic effects of opiates: clinical, neuroanatomical, and biochemical evidence. 696 53

The dopamine hypotheses of schizophrenia and antipsychotic drug action suggest that the dopamine metabolite homovanillic acid (HVA) should change with drug withdrawal and change in clinical state. We designed a study of cerebrospinal fluid (CSF), plasma, and urinary HVA on and off haloperidol to examine the effects of drug withdrawal. CSF and plasma HVA samples were obtained in 72 healthy schizophrenic (DSM-III-R) males (age: 36 +/- 7.4 years), before and after haloperidol withdrawal, which was after 6 weeks on placebo or sooner if they met specific criteria for relapse. We collected three 24-hour urine samples in 34 of these patients. In addition, CSF HVA was obtained in 24 well-screened age-matched male normal controls. HVA was measured with high-pressure liquid chromatography (HPLC). CSF HVA decreased significantly after drug withdrawal, particularly in those who met relapse criteria; drug-free CSF HVA levels were not significantly different from those of normals. Plasma HVA increased significantly after haloperidol withdrawal in relapsing patients, but not in clinically stable patients. Urinary HVA excretion decreased after withdrawal with decreased HVA clearance. We conclude that haloperidol withdrawal had a strong effect on dopamine turnover, whereas the patient's clinical state had only a weak central effect, without affecting total body production of HVA. Conceivably, dopamine involvement in schizophrenia reflects the failure of the homeostatic mechanisms that allow for integration of different functional brain components as needed.
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PMID:Dopamine turnover in schizophrenia before and after haloperidol withdrawal. CSF, plasma, and urine studies. 879 94


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