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 antipsychotic actions and extra-pyramidal side-effects of neuroleptic drugs are strongly correlated with their ability to block central dopaminergic transmission. It is argued that the former are more closely related to actions on dopaminergic mechanisms in the "mesolimbic dopamine" system, and the latter to similar actions in the striatum. Although the amphetamine psychosis closely resembles paranoid schizophrenia and may be due to excess dopamine release, clinical, biochemical, and endocrine studies suggest that dopaminergic overactivity is not a necessary concomitant of schizophrenic illnesses. It is suggested that the primary defect in schizophrenia does not lie in the dopamine neuron. It remains to be excluded that the receptors, particularly in the mesolimbic dopamine areas, become supersensitive, or that there is a deficit in a system which normally acts in antiagonism to the to the mesolimbic dopamine system.
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PMID:Dopamine and schizophrenia. 6 Jun 35

Amphetamine psychosis has been considered to be a pharmacologic model of schizophrenia. Fifteen previously reported cases were reviewed in which experimental induction of amphetamine psychosis occurred in nonschizophrenic drug abusers. Seven (possibly ten) cases manifested Schneider's first rank symptoms and all had World Health Organization Present-State Exam symptoms which discriminated schizophrenia. This observation draws further parallels between the phenomenology of amphetamine psychosis and schizophrenic symptoms.
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PMID:Amphetamine psychosis and psychotic symptoms. 11 94

A case is reported of a patient with carcinoid syndrome who developed a exogenous psychosis while under treatment with the serotonin-inhibitor p-chlorophenylalanine (PCPA). Partial symptoms similar to delirium and schizophrenia were exhibited. The attached literature survey focuses on the psychological side effects of PCPA treatment. A discussion follows concerning noteworthy phenomenological similarities between the case reported and certain forms of amphetamine psychosis. Common biochemical mechanisms are hypothetically stated.
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PMID:[Exogenous psychosis in a patient with carcinoid syndrome following treatment with p-chlorophenylalanine (PCPA)]. 13 50

1 The roles of catecholamine and 5-hydroxytryptamine (5-HT) release in mediating backward walking and circling were studied in rats. 2 These behaviours occurred in animals given 15 mg/kg intraperitoneally of (+)-amphetamine (which predominantly releases catecholamines) or either p-chloroamphetamine or fenfluramine (which predominantly release 5-HT). They also occurred when smaller doses of (+)-amphetamine (5 mg/kg) and either p-chloroamphetamine (2--5 mg/kg) or fenfluramine (5 mg/kg) were given together. 3 Characteristic dopamine-dependent behaviours (rearing, licking, gnawing) resulting from (+)-amphetamine injection were greatly reduced by p-chloroamphetamine or fenfluramine. 4 Characteristic 5-HT-dependent behaviours (wet dog shake, hind limb abduction) resulting from injection of either p-chloroamphetamine or fenfluramine were unaffected by (+)-amphetamine. 5 Fragmentary backward walking and circling resulting from levallorphan injection (50 mg/kg s.c.) were decreased by (+)-amphetamine at low dosage. 6 Results in general strengthen previous evidence that backward walking and circling are mediated by simultaneous dopamine and 5-HT release. 7 The possible relevance of the above findings to hallucinogenic activity, amphetamine psychosis, schizophrenia and abnormal movements due to L-DOPA treatment is discussed.
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PMID:Backward walking and circling: behavioural responses induced by drug treatments which cause simultaneous release of catecholamines and 5-hydroxytryptamine. 46 94

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

Three patients who abused ephedrine are presented. The clinical picture resembled that of schizophrenia and amphetamine psychosis. Its relevance to current theories on the aetiology and understanding of schizophrenia is discussed.
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PMID:Ephedrine abuse psychosis. 60

Some of the difficulties of trying to establish an animal model of schizophrenia are first considered. Then, after a review of the evidence on the experimental psychopathology of schizophrenia, particularly that concerned with attention and arousal, it is concluded that the core feature which needs to be modeled in animals is some aspect of "input dysfunction." It is argued that, of the pharmacological strategies, LSD-25 comes nearest to meeting that requirement, for two reasons. First, the phenomenology of an LSD "model psychosis" closely parallels that of the natural disease. Secondly, the experimental effects of the drug, both in animals and man, are very similar to or can be closely aligned theoretically with those of schizophrenia. An example is quoted from work in the author's laboratory where LSD was found to produce psychophysiological effects virtually identical to those observed occurring naturally in acute psychotic patients and in normal subjects high in "psychotic" personality traits. It is suggested that the rejection of LSD as a drug model was premature, especially as the currently popular preference for amphetamine has not been vindicated, either by the latter's ability to mimic an important central feature of the psychotic state or by work on dopamine as a specific common mediator of amphetamine psychosis and of schizophrenia.
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PMID:Animal models of schizophrenia: the case for LSD-25. 74 71

A case report of amphetamine psychosis in a 16-year-old female that closely resembled paranoid schizophrenia following the possible ingestion of a large quantity of amphetamine tablets is presented. The symptoms associated with amphetamine psychoses, the criteria used for differentiating amphetamine psychoses from schizophrenia, and the treatment of this drug-induced reaction are discussed. Treatment recommendation include the use of a dopamine antagonist such as haloperidol and the use of ascorbic acid to accelerate the renal elimination of amphetamines.
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PMID:Amphetamine psychosis. 90 Jan 38

Three main biogenic amine hypotheses for the origin of schizophrenia are discussed. The dopamine theory of schizophrenia postulates a pathogenetic connection between the disease and changes in the activity of dopaminergic cells in the brain. The theory is mainly based on findings on the mechanism of action of neuroleptics, on the clinical features and pharmacology of the amphetamine psychosis, and on some amphetamine effects in animals. Several results are in good agreement with the assumption of a state of hyperactivity of central dopamine neurons, whereas others, e.g. the lack of an increased dopamine turnover, are not. According to another theory, schizophrenia is caused by reversible damage to central norepinephrine cells. So far the only empirical basis for this theory is the finding that the activity of dopamine-beta-hydroxylase, a marker enzyme for noradrenaline cells, is lowered in the brains of schizophrenic patients. Thus further confirmation is required. The transmethylation hypotheses assume that hallucinogenic amine metabolites are produced in the body and lead to the appearance of schizophrenic symptoms. Whether or not the occurrence of DMPEA, presumably an oxymethylation product of the dopamine metabolism, is specific for schizophrenics is still open to question; if it is, the meaning of this finding is obscure. Current results leave open the possibility that N-dimethyltryptamine or other N-methylated hallucinogenic biogenic amine metabolites cause the disease; however, this hypothesis is hardly confirmed by positive empirical results.
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PMID:[Biogenic amines and schizophrenia]. 106 94

We have previously reported that, from a phenomenological standpoint, the behavioral manifestations of cats chronically intoxicated with amphetamine parallel the evolution of the paranoid psychosis induced by the drug in humans. However, certain manifestations in the cat, such as frozen postures, disjunctive behaviors and postures, cataleptic-like phenomena, obstinate progression, loss of righting reflex and pupillary changes, did not appear to be consistent with the phenomenology of the paranoid psychosis. Since treatment of schizophrenic patients with disulfiram, an inhibitor of norepinephrine synthesis that acts at the level of the enzyme dopamine beta-hydroxylase, thereby leading to increased dopamine concentrations, had been found to profoundly exaggerate psychotic symptomatology, amphetamine behavioral syndrome in the cat as it is modified by pretreatment with disulfiram. Following such pretreatment, a faster development of certain end-stage components of the amphetamine syndrome was obtained. Thus, on the first day, development of a Reactive attitude and of more prominent behavioral disjunction occurred with the combined drug administration as compared with amphetamine alone. In contrast with the facilitation of these behaviors was the absence of dyskinesias and hyperreflexia on that day. Stereotyped behavior, loss of motor initiative and hyperkinetic activity were markedly enhanced and appeared with a shorter latency period on subsequent days of the intoxication cycle. Loss of righting reflex was an early manifestation in these animals. During the later days, the particularly high level of compulsive activity was evident from the occurrence of an obstinate progression syndrome and the performance of stereotyped movements of the head in the presence of a crucifixion posture. In general, modification of the amphetamine effects on behavior was in a direction consistent with comparable features in experimental catatonia and the catatonic form of schizophrenia. The need to integrate such phenomena in any amphetamine model of psychosis is stressed and analogies are drawn with similar features reported in animals treated with bulbocapnine or other psychotogenic compounds and with symptoms of human amphetamine psychosis and schizophrenia.
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PMID:Effects of disulfiram on the amphetamine-induced behavioral syndrome in the cat as a model of psychosis. 124 12


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