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

Synthetic substance P has been discovered to stimulate significantly the formation of dopa in the limbic, striatum, hemisphere and diencephalon regions of the brain and the lower brain stem. There was no effect upon 5-hydroxytryptophan formation or on tryptophan or tyrosine levels. After inhibition of monoamine synthesis by N'-(DL-SERYL)-N2-(2, 3, 4-trihydroxybenzyl)hydrazine, substance P significantly accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine. Substance P appears to stimulate monoaminergic neurons in the brain and to serve as an excitatory transmitter in nerve terminals impinging upon dopaminergic cell bodies. A similar stimulation of noradrenaline and 5-hydroxytryptamine indicate a similar transmitter role for noradrenergic and serotonergic neurons. These data strengthen questions about the possible clinical influence of substance P in disease states involving monoaminergic mechanisms including Parkinsonism and schizophrenia.
 ...
PMID:Effect of synthetic substance P on monoaminergic mechanisms in brain. 0 76

The antipsychotic drugs have provided effective and relatively safe treatment of schizophrenia, paranoid illnesses, and manic-depressive conditions marked by psychotic features. These agents are sometimes called "neuroleptic," as virtually all produce signs of extrapyramidal neurologic disorders in addition to their antipsychotic actions; in part, evidently, the neuroleptic effects are an artifact of the means of screening of potential new agents. These agents have a strong and selective antagonistic action on synaptic mechanisms in the brain mediated by dopamine as a neurotransmitter. This antidopamine action almost certainly contributes importantly to their parkinsonism effect (basal ganglia) and their prolactin-elevating (hypothalamic) effect; in addition, antipsychotic actions may be mediated by antidopamine effects, possibly in limbic and other forebrain centers.
 ...
PMID:The "neuroleptic" antipsychotic drugs. 1. Mechanisms of action. 3 41

A study of anti-Parkinsonism agents in prolonged phenothiazine therapy seeks to clarify some anecdotal misconceptions. Antiparkinsonian agents do not appear to affect the therapeutic efficiency of phenothiazines, nor does using them on a "demand" basis increase the problems of control of parkinsonian side effects. Older patients, however, appear to require the extended usage of antiparkinsonian agents rather more than some studies would suggest. Sustained release antiparkinsonian agents may yet further simplify the management of schizophrenia.
 ...
PMID:Implications of phenothiazine side effects: a study of antiparkinsonian agents in an older population. 23 89

The need for medication with anticholinergic antiparkinsonian drugs was examined in 118 schizophrenic patients under long-term neuroleptic treatment. It was found that 1) none of 18 patients under treatment with low mg potency neuroleptics (chlorprothixene, clozapine, and thioridazine) had any need for anticholinergics; 2) of 60 patients under treatment with short-acting high mg potency neuroleptics (perphenazine greater than 16 mg daily and haloperidol greater than 2 mg daily) nine patients (15%) required medication with anticholinergics, whereas 3) of 40 patients under treatment with long-acting (depot) neuroleptics, 17 (43%) had a need for anticholinergic medication; and 4) no patient factors predisposing to the need for continued antiparkinsonian treatment could be identified. In an additional double-blind cross-over study of 12 patients presenting persisting neuroleptic-induced parkinsonism, it was found that G 31.406 (a new potentially antiparkinsonian drug), compared with placebo, had an antiparkinsonian effect (P less than 0.01) as well as an antidepressant effect (P less than 0.05). G 31.406 resulted in an improvement in anxiety and schizophrenia-score in some patients. Compared with placebo, orphenadrine had a more questionable effect on parkinsonism (0.05 less than P less than 0.01) and no significant effect on mental symptoms. There were no significant differences between the effects of G 31.406 and orphenadrine.
 ...
PMID:Antiparkinsonian agents and long-term neuroleptic treatment. Effect of G 31.406, orphenadrine, and placebo on parkinsonism, schizophrenic symptoms, depression and anxiety. 32 38

Clinical and neuropharmacological evidence indicates the involvement of dopaminergic mechanisms in Parkinson's disease and schizophrenia, as well as in iatrogenic Parkinsonism and drug-induced schizophrenia-like syndrome. The evidence hitherto presented stresses the existence of a reversed relationship between Parkinson's disease and schizophrenia and implicates the possibility that dysfunction of dopamine-receptors may be a central phenomenon in both diseases. In view of the recent demonstration of two separate dopamine-receptors, it is postulated that a striatal receptor blockade may cause Parkinson's disease, whereas a limbic receptor blockade may result in schizophrenia. The recent discovery that several autoimmune diseases, such as myasthenia gravis, are the result of an immunopharmacological block at receptor sites, together with several observations of immunological disorders in Parkinson's disease and schizophrenia, suggests the possibility that certain types of Parkinson's disease and schizophrenia might be the consequence of an autoimmune blockade of striatal or limbic dopamine-receptors, respectively.
 ...
PMID:Automimmune response to dopamine-receptor as a possible mechanism in the pathogenesis of Parkinson's disease and schizophrenia. 73 51

Through the study of the pharmacological and clinical actions of chlozapine, a new drug used in psychiatry, we are questioning one of the traditional statements on the therapeutic action of antipsychotics: the affirmation that those must have, concomitantly, antipsychotic action and intense extrapyramidal effects (drug-induced parkinsonism). Combining our own investigations and those of other authors, the generally accepted concepts on the possible biochemical mechanisms involved in the etiology of endogenous psychosis are criticized. Although there is evidence of alterations of the dopaminergic system in schizophrenia and also changes due to the action of neuroleptics, we cannot reject, given the dissociation of effects obtained with chlozapine, the possibility that the repercussion on the nigrostriatal dopaminergic system be only one of the many probably mechanisms of action of psychotropic drugs. Thus, such anatomical and neurochemical systems could be involved only in a secondary manner in the biochemical alterations typical of schizophrenia.
 ...
PMID:Pharmacopsychiatry and iatrogenic Parkinsonism. 93 Jul 44

It is now well recognized that the hypothalamus is an important site of neuropathology in Parkinson's disease (PD). Lewy bodies, a marker of nerve cell degeneration and a pathological hallmark of PD, have been observed frequently in the hypothalamus of PD patients by Lewy (1923) and other investigators and confirmed by more recent systematic studies by Langston & Forno (1978). Both Lewy and Langston & Forno found a predilection of Lewy body formation in specific hypothalamic nuclei with the tuberomammillary, lateral, and posterior areas containing by far the highest average counts per nucleus. Selective vulnerability of the tuberomammillary, lateral, and posterior hypothalamic cell groups to degeneration has been observed also in aging, postencephalitic Parkinsonism, Alzheimer's disease, and schizophrenia. The susceptibility of these particular nuclei to degenerative changes including Lewy body formation is not presently understood nor are the mechanisms by which Lewy bodies are formed in PD and other CNS disorders. Accumulation of amines, a pathological process which follows degeneration of catecholamine-containing neurons in experimental animals, also occurs most frequently in the lateral and posterior hypothalamic areas. In the present communication we propose that in PD, amine accumulation may be a precursor to Lewy body formation and that the susceptibility of certain hypothalamic areas to Lewy body formation may be related to their propensity to accumulate amines. Furthermore, the frequent co-existence of Lewy bodies and Alzheimer's neurofibrillary tangles in the lateral and posterior hypothalamic nuclei suggest that they may share a common pathogenetic etiology. If confirmed, this hypothesis may provide an experimental model by which the formation of Lewy bodies and neurofibrillary tangles may be investigated.
 ...
PMID:Amine accumulation: a possible precursor of Lewy body formation in Parkinson's disease. 130 71

Investigations aimed at identifying the clinical characteristics that discriminate tardive dyskinesia (TD) from non-TD patients have yielded disparate findings. We have suggested, based on pharmacological and neuroradiological studies, that TD in schizophrenia may be a covariate of positive symptoms while drug-induced parkinsonism (DIP) may relate to negative symptoms. To investigate this hypothesis, we examined in 47 institutionalized schizophrenic patients the relationship of TD and DIP with psychopathology clusters rated on the Positive and Negative Syndrome Scale. We found that involuntary movements of TD were significantly associated with the activation cluster (p < .01), whereas DIP was significantly associated with the anergia cluster (p < .01). These findings thus support the position that TD is a specific facet of the positive syndrome in schizophrenia, while DIP is a specific feature of the negative syndrome. Clinically, the data suggest that schizophrenic patients with predominant positive symptoms may be at increased risk for TD, while those with prominent negative features could be at increased risk for DIP. In analogy with the positive/negative dichotomy, we propose that TD could be regarded as a "positive," while DIP as a "negative" movement disorder.
 ...
PMID:"Positive" and "negative" movement disorders in schizophrenia. 130 14

A distinct hypokinetic syndrome appears to exist across several different neuropsychiatric diagnoses, involving (1) slowed motor activity with difficulty initiating and sustaining behaviors, (2) anhedonia with depressed mood and reduced affective range, and (3) cognitive impairment. Specifically, three well-recognized states--parkinsonism, retarded depression, and the negative symptoms of schizophrenia--prominently feature the components of this syndrome, and reduced dopamine turnover in the brain has been hypothesized to play a part in the pathophysiology of each. While aspects of this conceptualization remain controversial, it generates testable hypotheses that could have implications for the understanding and treatment of these states.
 ...
PMID:Akinesia: a syndrome common to parkinsonism, retarded depression, and negative symptoms of schizophrenia. 135 15

Three phenomena concerning the antipsychotic action of classic neuroleptic drugs have not been adequately explained by the dopamine hypothesis: (1) administration of neuroleptic drugs is commonly associated with an initial period of 3-6 weeks prior to demonstration of antipsychotic effects; (2) similarly, neuroleptic-induced Parkinsonism commonly emerges only after several weeks of neuroleptic therapy; (3) moreover, Parkinsonism may disappear despite continuous neuroleptic treatment. An understanding of these phenomena might shed new light into the nature of the antipsychotic actions of these agents, and hence the pathophysiology of schizophrenia. We propose that the increase in melatonin secretion, which occurs with the initiation of neuroleptic therapy, may be responsible for the delay in the antipsychotic effects of neuroleptics and may also account for the lag in the development of drug-induced Parkinsonism as well as its disappearance. The implications of this hypothesis for the treatment of schizophrenia and the prophylaxis of drug-induced Parkinsonism are discussed.
 ...
PMID:The role of melatonin in the antipsychotic and motor-side effects of neuroleptics: a hypothesis. 136 41


1 2 3 4 5 6 7 8 9 10 Next >>