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)

Different ergot structures (lumilysergol and lysergol) were chlorinated or brominated in the position 2, and the development of antidopaminergic activity was studied. The tested 2-halo-lysergols exerted neuroleptic-like action indicated by the suppression of conditioned avoidance response (CAR), and other effects characteristic of dopamine antagonists (cataleptogenic effect, prevention of amphetamine-induced toxicity, inhibition of L-DOPA-induced hyperactivity, lowering of spontaneous body temperature, antagonism of apomorphine-induced hypothermia). A second halogen substitution in the position 8 of the lysergol structure left the CAR suppression activity untouched, but abolished other dopamine antagonistic effects. This unique psychopharmacological profile refers to potential usefulness of the compounds in schizophrenia, and at the same time perhaps in particular forms of Parkinson's disease or tardive dyskinesia.
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PMID:Substituted ergolines: potential antipsychotics with unique profile. I. Psychopharmacological characterization. 290 63

In summary, we have reviewed rCBF data in humans that suggest that mesoprefrontal dopaminergic activity is involved in human cognition. In patients with Parkinson's disease and possibly in patients with schizophrenia, prefrontal physiological activation during a cognitive task that appears to depend on prefrontal neural systems correlates positively with cognitive performance on the task and with clinical signs of dopaminergic function. It may be possible in the future to examine prefrontal dopamine metabolism directly during prefrontal cognition using positron emission tomography and tracers such as F-18 DOPA.
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PMID:Mesocortical dopaminergic function and human cognition. 297 64

In dogs, the influence of chronic administration of the agonist (L-DOPA) and antagonist (haloperidol) of central dopamine processes on functional interrelations of the brain structures was studied by dynamics of evoked potentials. Cortical-subcortical relations during formation of a motor habit are described in intact animals: basic functional regimes of central integration are singled out--sensory and motor one. Change of their equilibrium is the general principle of systemic reconstructions elicited by differently directed interferences in dopamine processes. Against the background of chronic administration of haloperidol, a sensory-motor imbalance is formed due to uniform functioning of the basal ganglia as analyzer of the signal stimulus; simultaneously the utilization of afferentation elicited by the movement is limited. A variant is revealed of intercentral relations corresponding to bradykinesia development. Under chronic administration of L-DOPA, interrelations of sensory and motor regimes become competitive; basal ganglia are provided with nontypical kinds of afferentations. Intercentral relations variant is examined corresponding to development of psycho-motor excitation. The results are discussed in connection with pathogenic and compensatory mechanisms of some symptoms of parkinsonism and schizophrenia.
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PMID:[Principle of reorganizing the functional interrelations of brain structures in action on the dopamine system of dogs]. 343 33

Psychiatric disorders induced by drugs are of most concern when they occur in the context of therapeutic use of a drug. Such iatrogenic psychiatric disturbances may interfere considerably with the treatment of the primary illness and may cause concern to patients, their relatives and the medical staff. Because many drugs are often used simultaneously in seriously ill patients, it may be difficult to be sure which drug may have been responsible. The best procedure is to remove those drugs which are most probable causes of the psychiatric disturbances as well as any drugs that are not truly essential for the treatment of the patient. Problems involved in evaluating the relationship between use of drugs and psychiatric disorders are considerable. Many reports are isolated cases and the denominators which might provide some idea of the potential risk are unknown. Many relationships are still controversial, such as the association of depression with sedatives, antihypertensives and oral contraceptives. Areas of uncertainty are great. Psychomotor impairment may be caused by a drug that can alter consciousness, or any drugs that can produce more delineated psychiatric syndromes. Sedative drugs are those most commonly associated with psychomotor impairment, and may include psychotherapeutic drugs, sedative antihistamines, narcotic analgesics and, of course, the widely used social drug, alcohol. Delirious states are most often associated with drugs that possess central anticholinergic actions. These include not only drugs clearly identified as anticholinergics, but also tricyclic antidepressants and anti-Parkinson drugs. Cimetidine, which is often used parenterally in seriously ill patients, is also a prominent cause. Delirium is most often seen in elderly patients and in those who have received rather large doses of drugs. The association of schizophrenic-like psychoses with dopaminomimetic drugs tends to support the prevailing dopamine hypothesis of schizophrenia. Levodopa, the dopamine precursor, and bromocriptine, a direct dopamine agonist, are examples of such relationships. Abuse of social drugs has also been thought to provide a useful model of schizophrenia. Hallucinogens are probably a rather poor model, abuse of amphetamines may provide a better model, and possibly the best is the psychotic state elicited by phencyclidine. Manic reactions are clinically difficult to differentiate from schizophrenic-like psychoses and are often produced by similar drugs. Corticosteroids may produce either manic or schizophrenic-like disorders, as well as occasionally confusion and depression.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Drug-induced psychiatric disorders and their management. 354 May 20

Studies on the treatments for neuroleptic-induced tardive dyskinesia published in the literature are reviewed. The great number of different treatments and the controversial results of most studies show that there is as yet no specific and safe treatment for tardive dyskinesia. Suggestions for well-designed treatment studies are given: Placebo-controlled double-blind design, larger patient populations, clear diagnostic and standard observing and rating conditions using different assessment methods and videotapes, withdrawal of neuroleptics and antiparkinsonian drugs to discover reversible tardive dyskinesia. If this procedure is not feasible, neuroleptics and other drugs should be maintained at a stable dose level. Longer term studies of some months are necessary to study the prolonged efficacy of different drugs. The effect of dopamine-antagonists such as neuroleptics and of dopamine-depleting agents such as reserpine and oxypertine is of limited duration. Dopamine-agonists such as L-Dopa, bromocriptine and amantadine help only few patients and may even aggravate the symptoms of tardive dyskinesia. In some double-blind studies cholinergic drugs such as lecithin and deanol have improved tardive dyskinesia, but further controlled studies are needed. Anticholinergic drugs such as antiparkinsonian agents should not be prescribed because they may aggravate tardive dyskinesia. Some patients respond to GABA-ergic agents such as baclofen, sodium valproate and the benzodiazepines, but further studies are needed before the value of GABA-ergic agents in the treatment of tardive dyskinesia can be properly assessed. After withdrawal of neuroleptics the average of remission rates within a year is 20%-30%. Elderly patients are more likely to have persistent dyskinesias. A progressive stepwise diminution of the neuroleptic dose and of the antiparkinsonian agents is recommended. When a patient's psychosis is exacerbated after withdrawal of the neuroleptics and tardive dyskinesia is also present, small doses of thioridazine, clozapine or tiapride can be administered. If this practice is not successful cholinergic or GABA-ergic agents may be useful. Because no currently available therapeutic agents satisfies the criteria of safety, marked effectiveness and prolonged efficacy in the treatment of tardive dyskinesia, prevention becomes more important. Prolonged use of a neuroleptic medication requires careful evaluation of indications and risks. The doses of neuroleptic drugs during the maintenance treatment of schizophrenia should be as small as possible.
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PMID:[Therapeutic measures in tardive dyskinesia]. 613 57

The neurotransmitter dopamine has biological attributes that make it amenable to study by positron emission tomography, unlike many of the 40 or so neurotransmitters that have been identified in the brain. Dopamine deficiency in the nigrostriatal system is a characteristic of Parkinson's disease, and a disturbance of dopamine metabolism is still widely held to be responsible for the syndrome of schizophrenia. Despite its importance in the regulation of locomotion and mood, it has been impossible to visualize the intracerebral distribution of dopamine and measure its regional metabolism in man. In the first demonstration of the regional distribution of a neurotransmitter in the brain of conscious normal man, we show here that L-3,4-dihydroxyphenylalanine (L-dopa) labelled in the 6-position with the positron-emitting radionuclide fluorine-18, localizes specifically in the dopaminergic pathways of the human brain where its turnover could be measured atraumatically by positron emission tomography.
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PMID:Dopamine visualized in the basal ganglia of living man. 660 27

A 30-fold increase in excretion of L-DOPA, distinct elevation in synthesis of dopamine and noradrenaline as well as inhibition of adrenaline synthesis occurred in schizophrenic patients at an acute period after administration of 0.1 g of L-DOPA per os (L-DOPA test). As shown by the L-DOPA test, excretion of L-DOPA was distinctly decreased in the patients with the remittence step as compared with the acute period. At the same time, in the remission synthesis of dopamine occurred mainly in the night time, synthesis of noradrenaline was decreased as compared with the acute period. synthesis of dopamine was increased 8-fold both in the patients at the acute period (mainly in the day-time) and within the remittence period (in the night-time) of the disease. The variations in excretion of L-DOPA, dopamine and noradrenaline, found in schizophrenic patients, were markedly distinct from dynamics of these patterns in healthy adult persons but were more similar to the parameters characteristic for persons in old and senile age. The L-DOPA test developed might be used for diagnosis of schizophrenia and of its periods (acute period and remission).
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PMID:[Effect of a test with 0.1 g of L-DOPA on the dynamics of urinary excretion of catecholamines and DOPA in schizophrenic patients]. 677 21

Peculiarities of dopamine metabolism were investigated in 27 patients with various forms of active schizophrenic process. The investigations were carried out by determining the content of dopamine and its metabolites in the blood and urine. In all the patients a considerable rise of the dopamine blood level (284.7 of normal) was revealed: prevalent were bound forms of this amine. The free dopamine content in the blood rose still higher in cases of psychomotor excitation. The dopamine content in the patients' urine was lowered. The determinations of dopamine metabolites, such as, dihydroxyphenylacetic acid, and homovanillic acid showed an insufficiency of dopamine deamination: this was an evidence of a deficient activity of monoamine oxidase. Administration of L-DOPA to schizophrenic patients did not cause a rise of the dopamine blood level (in distinction from normal). The author suggests that the discovered disturbances of dopamine metabolism play a certain role in the pathogenesis of schizophrenia.
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PMID:[Various features of dopamine metabolism in schizophrenia]. 679 91

The purpose of this study was to determine the plasma level of clozapine and its metabolite, N-desmethylclozapine, in Parkinson's disease patients with L-DOPA-induced psychosis responsive to clozapine. The psychotic symptoms of the three patients studied responded to low doses of clozapine with plasma levels of clozapine between 4.5 and 16.1 ng/ml and N-desmethylclozapine between 2.6 and 6.1 ng/ml, much below the plasma clozapine levels usually found in clozapine-treated refractory schizophrenia or affective disorders (range 100 to 687 ng/ml). Possible mechanisms that may account for clozapine's antipsychotic action in dopaminomimetic-induced psychosis in Parkinson's disease, including serotonin2A (5-HT2A) and dopamine D4 receptor blockade, at plasma levels that would be ineffective in refractory schizophrenia, are discussed. It is suggested that 5-HT2A receptor blockade is the most likely basis for the effectiveness of clozapine in L-DOPA psychosis.
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PMID:Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson's disease. A high potency effect of clozapine. 776 85

In the first section of this paper several aspects of tardive dyskinesia (TD) (clinical, epidemiological, pharmacological) are reviewed. We propose that this syndrome is not the consequence of dopamine receptor proliferation, but results from damage or degeneration of striatal cholinergic interneurons. We suggest that this cellular damage is caused by prolonged overactivation of these neurons, which occurs when they are released from dopaminergic inhibition following neuroleptic administration. Overactivity of central cholinergic systems during akinetic and motor retarded depression could be a contributory cause. The predisposition to L-DOPA-induced peak-dose dyskinesia in Parkinson's disease may depend on the same type of striatal neuronal loss. In the second part of the paper, the subject of supersensitivity psychosis and drug-resistant schizophrenia is reviewed. These two syndromes, are commonly associated with TD, have similar predisposing factors and pharmacology to TD, and are potentially persistent. We suggest that these conditions also result from degeneration of cholinergic striatal interneurons following chronic neuroleptic administration. The efficacy of clozapine for such treatment-refractory psychoses is explained in terms of its blockade of D-1 dopamine receptors. Other drugs effective against refractory psychoses (e.g. risperidone) are predicted to reduce activation at D-1 receptors.
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PMID:Loss of striatal cholinergic neurons as a basis for tardive and L-dopa-induced dyskinesias, neuroleptic-induced supersensitivity psychosis and refractory schizophrenia. 790 33


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