Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies are reported of the variation of melatonin in serum, plasma urine and cerebrospinal fluid in normal subjects and in patients with various diseases. The diurnal variation of plasma and urine melatonin found in healthy controls on a regular dark-sleep pattern persisted when the subjects slept in light. The effect of sleep deprivation and of rapid light exposure at night is reported. There was a correlation between melatonin in morning urine and plasma at 2 a.m. Four hours of extended darkness in the morning as well as a 9-hour shift of sleep and activity cycles following travel affected the melatonin rhythm. The night increase in plasma melatonin preceeded both the cortisol and prolactin rise. A single oral dose of 4.3 X 10(5) nmol of melatonin given to a 44-year-old healthy male gave a peak plasma value of 624 nmol/l after 30 min. Plasma melatonin was not affected by electroconvulsive therapy, TRH-injection, L-Dopa or bromoergocryptine orally. Patients with alcoholism, migraine, postoperative pinealoma, panhypopituitarism, hereditary dystonia and schizophrenics on propranolol exhibited a decreased amplitude of their diurnal rhythm of melatonin. Two patients with pituitary tumors had occasional high levels of plasma melatonin. The change in melatonin secretion in human is apparently controlled by a mechanism which is at least party influenced by environmental lighting conditions, drugs and different disease states.
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PMID:Melatonin in humans physiological and clinical studies. 38 89

Measurements were made of the content of gonadotropic pituitary hormones (prolactin/PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol in 151 children aged 11 to 15 years. Of these, there were 58 healthy children (24 boys and 34 girls), 51 children (25 boys and 26 girls) with vegetovascular dystonia (VVD) of the vagotonic type and 42 children (22 boys and 20 girls) with VVD of the sympathotonic type. It has been established that in VVD children, alterations in the hypothalamus-pituitary-gonadal system agreed with the general biological reactions of the body, while deviations in the LH and FSH levels as well as in estradiol got stabilized by 13 to 15 years. A positive correlation has been revealed between the high blood PRL level and the high tone of the sympathetic nervous system. In view of this fact the blood PRL content can serve an early diagnostic test for recognizing hypersympathicotonia in VVD children.
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PMID:[Significance of the determination of gonadotropic pituitary hormones in different types of autonomic vascular dystonia]. 190 69

(5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(2-fluorophenyl)methanone (1) was found to have an antipsychotic-like profile in behavioral tests predictive of antipsychotic efficacy but, unlike available antipsychotic agents, did not bind in vitro to dopamine receptors. Upon further evaluation, 1 was found to cause clonic seizures in aged rodents. An examination of related structures revealed that 5-(substituted aminoacetamide) analogues of 1 shared this novel pharmacology and did not cause seizures. The synthesis and pharmacological evaluation of this series of compounds are described. Two compounds, 2-(diethylamino)acetamide (25) and 2-[[3-(2-methyl-1-piperidinyl)propyl]-amino]acetamide (38), were selected for examination in secondary tests. Like known antipsychotics both compounds reduced spontaneous locomotion in mice at doses that did not cause ataxia and inhibited conditioned avoidance selectively in both rats and monkeys. Unlike known antipsychotics neither 25 nor 38 elicited dystonic movements in haloperidol-sensitized cebus monkeys, a primate model of antipsychotic-induced extrapyramidal side effects. Biochemical studies indicated that these compounds act via a nondopaminergic mechanism. Neither 25 nor 38 bound to dopamine receptors in vitro or caused changes in striatal dopamine metabolism in vivo. In addition, they did not raise serum prolactin levels as do known antipsychotics. Although adverse animal toxicological findings have precluded clinical evaluation of these agents, the present results indicate that it is possible to identify at the preclinical level nondopaminergic compounds with antipsychotic-like properties.
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PMID:(5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(2-fluorophenyl)methanones . A series of novel potential antipsychotic agents. 287 84

This review discusses several aspects of epilepsy and sleep. The level of wakefulness is controlled by transmitters such as acetylcholine, norepinephrine, serotonin, and histamine. These neurotransmitters are involved in modulatory neurotransmission of the ascending brain stem systems, which play an important role in controlling the sleep-wake cycle. Experimental evidence suggests that rapid eye movement sleep atonia is induced by increased endogenous acetylcholine release. Regarding sleep factors, recent data suggest that prolactin may stimulate rapid eye movement sleep and that growth hormone-releasing factor is involved in non-rapid eye movement sleep regulation. The neuropharmacologic features of several animal models of epilepsy have been investigated. Epileptiform discharges of genetic absence seizures in rats have been found to be suppressed by cholinergic drugs. The beta-carboline abecarnil has a strong antiepileptic effect on spike-wave discharges in rats that generate spontaneous spike-wave discharges, and it may be useful as an antiepileptic drug. Sleep epilepsy has been studied in a model of amygdala-kindled kittens. During the postkindling development, multifocal epilepsy with convulsions occurred that were distributed throughout the sleep-wake cycle; this finding agrees with the clinical literature. A typical feature of juvenile myoclonic epilepsy is the occurrence of seizures in a strict relationship to the sleep-wake cycle. There is now some neurophysiologic evidence that this syndrome also causes disturbance of sleep stability with increased arousal reactions. Nocturnal paroxysmal dystonia is not a homogeneous entity. Several clinical reports indicate that the short-lasting variant is most likely a form of frontal lobe epilepsy, but the nature of the longer-lasting variants is still obscure.
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PMID:Epilepsy and sleep. 791 13

We report a 68 year old man with a 7 year history of Parkinson's disease (PD) who obtained little benefit from treatment by dopaminergic and anticholinergic agents. During the six months prior to presentation, he experienced more rapid deterioration in symptoms including memory functions, increasing depression, and dystonia of the foot. External application of picoTesla range magnetic fields (MF) resulted in rapid attenuation of tremor and foot dystonia with improvements in gait, postural reflexes, mood, anxiety, cognitive, and autonomic functions. Plasma prolactin and luteinizing hormone (LH) levels rose three days after initiation of treatment. In addition, distinct electroencephalographic (EEG) changes were recorded nine days after two treatments with MF and included enhancement of alpha and beta activities as well as resolution of the theta activity. These findings demonstrate, for the first time, objective EEG changes in response to picoTesla range MF in PD. Since the pineal gland is a magnetosensor and as some of the clinical effects produced by MF such as relaxation, sleepiness, mood elevation, increased dreaming, and enhancement of alpha and beta activities in the EEG have also been noted in healthy subjects administered melatonin, we propose that the clinical effects as well as the EEG changes noted after treatment with MF were mediated by the pineal gland which previously has been implicated in the pathophysiology of PD.
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PMID:The effects of external picoTesla range magnetic fields on the EEG in Parkinson's disease. 808 28

Olanzapine is a thienobenzodiazepine derivative which displays efficacy in patients with schizophrenia and related psychoses. It has structural and pharmacological properties resembling those of the atypical antipsychotic clozapine and an improved tolerability profile compared with the classical antipsychotic haloperidol. In several large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine generally 5 to 20 mg/day was at least as effective as haloperidol (5 to 20mg) and more so than placebo, as assessed by overall rating scales for psychoses. Olanzapine improved negative symptoms to a greater extent than haloperidol in 2 of 3 comparative trials, including the largest trial. Efficacy of olanzapine has a rapid onset (within 1 to 2 weeks). Its clinical benefits appear to be maintained for treatment periods of up to 1 year, as shown by analysis of the extension phase of several trials demonstrating decreased probability of hospitalisation over this period compared with haloperidol. Preliminary data suggest the drug may also improve quality of life. Olanzapine was associated with significantly fewer adverse movement disorders (e.g. akathisia, dystonia, hypertonia, extrapyramidal symptoms) than haloperidol. There have been no reports of agranulocytosis (as occurs with clozapine) or any other haemotoxicity attributed to olanzapine, and the drug has shown minimal effect on prolactin levels. Transient increases in levels of hepatic transaminases seem to be clinically important. The only events recorded more frequently during olanzapine than during haloperidol therapy were weight gain, dry mouth and increased appetite. Although the antipsychotic activity of olanzapine has been well demonstrated. Its efficacy in refractory schizophrenia and its place relative to other atypical antipsychotics remain to be determined. Nevertheless, if the long term tolerability profile of olanzapine is confirmed, the drug should provide a valuable therapeutic alternative in the management of schizophrenia and related psychoses.
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PMID:Olanzapine. A review of its pharmacological properties and therapeutic efficacy in the management of schizophrenia and related psychoses. 902 46

The occurrence of acute dystonia was prospectively monitored in 39 schizophrenic patients (18 male and 21 female) treated with 9 to 27 mg/day of nemonapride, a selective dopamine antagonist, and the relationship of acute dystonia with characteristics of patients and plasma concentrations of the drug and prolactin was investigated. Twenty (51.3%) of 39 patients had dystonic reactions, the onsets of which occurred within 3 days after the initiation of treatment in 90% of dystonic patients. The incidence of acute dystonia was significantly higher in male than in female patients (77.8% vs. 28.6%, p < 0.05). Younger male patients (< or = 30 years) especially had an extremely high incidence of this side effect (91.7%). A positive correlation between prolactin response after 1 week of treatment and dystonia rating scores was found in male (Spearman rank correlation: r(s) = 0.606,p < 0.01) but not in female patients (r(s) = -0.378,p = not significant). These results suggest that young male patients have the highest risk of neuroleptic-induced dystonia. Prolactin response after 1 week of treatment as an index of dopamine blockade may reflect vulnerability to the development of acute dystonia at least in male patients treated with nemonapride.
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PMID:Characteristics and risk factors of acute dystonia in schizophrenic patients treated with nemonapride, a selective dopamine antagonist. 993 42

Our experience with atypical antipsychotics in patients with PD is that their motor effects are not predictable. The multiple reports concerning clozapine's beneficial effects on tremor, dystonia, nocturnal akathisia, and dyskinesias all underscore this observation. However, the appearance of even minor degrees of parkinsonism in normal volunteers or schizophrenics should suggest that an antipsychotic will not be well-tolerated in patients with PD. The treatment of PD is probably the most stringent test of a drug's freedom from parkinsonian side effects. The data from trials in schizophrenia concerning parkinsonian effects cannot always be confidently interpreted. Virtually all subjects in these trials have been treated with typical neuroleptics until shortly before study entry. Because the parkinsonian side effects of these drugs may persist for several months, patients may still show declining levels of parkinsonism even when placed on a drug that induces it if this effect is milder than that induced by the pre-study neuroleptic. Depending on the pre-study drug used and the duration of the study, distinguishing placebo from a low-potency neuroleptic may be impossible. Furthermore, the standard measure of parkinsonism in psychiatric studies is the Simpson-Angus scale which is heavily weighted toward rigidity and may underscore bradykinesia, gait, and posture abnormalities. The prolactin response to an antipsychotic drug may turn out to be a good predictor of its freedom from parkinsonian side effects. That would fit with the data presented above of clozapine and quetiapine having less parkinsonian effects, olanzapine having more but variable effects and risperidone being poorly tolerated. With the data presented above, comprising a current review of all reports of the use of atypical antipsychotics in PD that we could locate, we can say little with certainty. The only drug with confirmed benefit without worsening parkinsonism is clozapine. Open-label trials involving over 400 patients and two multicenter, placebo-controlled, double-blind trials have demonstrated that it is effective in treating the psychosis. It improves tremor, does not worsen other motor functions to any significant extent, and is safe at low doses. Limited data provide conflicting information on both risperidone and olanzapine. Quetiapine seems to be well-tolerated with some, but definitely less, worsening of PD motor features than risperidone and olanzapine. Based on the current literature, our personal experience, and anecdotal experience of other PD specialists which we solicited, we will venture our own interpretation and recommendations. We think risperidone is poorly tolerated and should be used only as a last resort; that olanzapine is better than risperidone but will, in a majority of patients with PD, worsen motor function. We are optimistic, but not yet convinced, that quetiapine may prove to be as effective and better tolerated than clozapine. It will not require cumbersome monitoring because it does not induce a blood dyscrasia. We therefore recommend that DP be treated in the following manner. First, the anti-PD medications should be simplified and reduced as much as tolerated. We think, in general, side effects multiply more with increasing numbers of drugs than with drug dose, so that patients are more likely to tolerate a higher dose of levodopa than a lower dose of levodopa combined with other adjunctive anti-PD medications. In reducing anti-PD medications, we recommend tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. Anticholinergics are stopped first, then selegiline, dopamine agonists, amantadine, and finally COMT inhibitors, which have no psychotomimetic action of their own. Finally, levodopa is reduced. Generally, a point is reached at which the anti-PD medications cannot be reduced without jeopardizing motor function. If psychosis persists at this point, then an antipsychotic is added. (ABS
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PMID:Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease. 1075 67

The cardinal feature of traditional neuroleptic drugs is extrapyramidal symptoms (EPS), such as parkinsonism, akathisia, and dystonia. Irrespective of the autonomic nervous system side-effect profile of a specific neuroleptic, the entire class produces EPS. Therefore, EPS and antipsychotic activity were once thought to be inextricably linked. However, with the discovery of clozapine, this concept was no longer defensible. Clozapine produced antipsychotic actions without associated EPS or increases in serum prolactin levels, and the term 'atypical' was coined to differentiate its actions from those of the traditional agents. Later, the definition of atypical was expanded to encompass clozapine's unique clinical spectrum of activity, including its effectiveness in treating some patients unresponsive to traditional neuroleptics. Clozapine thus became the archetype for a new generation of antipsychotic drugs, which now includes quetiapine, olanzapine, risperidone, sertindole, ziprasidone, zotepine and amisulpride. This paper will review the pharmacological actions that contribute to the unique features of clozapine, focusing on receptor profile and activity in animal models used for evaluations of antipsychotic activity and EPS. Similarities and differences amongst the new agents will also be discussed. Although conclusions regarding atypicality require controlled clinical trials in addition to preclinical and animal models, it is apparent from this review that not all agents match the profile of clozapine.
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PMID:The new generation of antipsychotic drugs: how atypical are they? 1134 14

Associations between neuroleptic side effects and plasma concentrations of the drug and prolactin were investigated in 33 acutely exacerbated schizophrenic patients (16 males and 17 females) treated with a fixed dose of nemonapride (18 mg/day), a new substituted benzamide, for 3 weeks. The most frequently observed side effects during nemonapride treatment were extrapyramidal symptoms such as akathisia (69.7%), dystonia (48.5%), hypokinesia (45.5%), tremor (39.4%) and increased salivation (36.4%). There were positive correlations between prolactin response and extrapyramidal side effects (EPS) scores after 1 week (Spearman rank correlation rs=.651, P<.01), 2 weeks (rs=.567, P<.05) and 3 weeks (rs=.670, P<.01) in male patients although no significant correlations were found in female or total patients. No significant correlations were found between plasma concentrations of the drug and total or any subscale side effects scores. The present study thus suggests that the spectrum of nemonapride-induced side effects is characterized by predominant extrapyramidal symptoms, and that prolactin response as an index of dopamine blockade reflects severity of EPS at least in male patients treated with nemonapride.
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PMID:Associations between side effects of nemonapride and plasma concentrations of the drug and prolactin. 1181 5


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