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)

Haloperidol treatment for stuttering was examined in a double-blind cross-over study of 26 adult volunteers with long-standing stuttering. Most had had unsuccessful speech and drug therapy. During the three-month study, their speech and stuttering patterns were repeatedly evaluated from videotaped readings of a standard passage and during spontaneous speaking. Of the 18 patients completing the trial 11 were significantly more improved on haloperidol than on placebo, three benefited equally from both, and four were unchanged. Improvement over placebo was indicated by fewer dysfluencies, increased speed of speaking, and reduced secondary "struggle" phenomena. Side effects were common on a dosage of 3 mg haloperidol daily. Poor concentration, akathisia and dystonic movements caused 8 patients to discontinue the trial despite significant improvement in 5 of them. Although "statistically significant" improvement occurred in most patients on haloperidol, the "clinical significance" of this form of therapy will be limited by the partial response, the need for continuous medication, the side effects of haloperidol and the attitude of stutters to this type of therapy.
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PMID:Haloperiodl in the treatment of stuttering. 32 82

Haloperidol (0.25 mg/kg i.m.) was injected daily for 6 months in six normal monkeys. Over a 24 hour period, the following symptoms could be observed: akathisia, circling, akinesia, choreoathetoid and dystonic movements, oro-facial dyskinesias and postural tremor with or without harmaline. Six months after cessation of haloperidol, harmaline-induced postural tremor could still be observed in all animals and oro-facial abnormal movements, in one monkey. The neuropathologic study of the experimental material did not disclose any alteration of the central nervous system.
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PMID:Haloperidol-induced dyskinesias in the monkey. 40 96

The traditional (typical) neuroleptic drugs produce acute extrapyramidal symptoms (EPS) in the majority of patients, whereas the atypical neuroleptics produce only minimal motor system side effects. Studies of acute dystonia in nonhuman primates with typical (haloperidol, fluphenazine), atypical (clozapine), and putative novel antipsychotic compounds with low EPS (remoxipride, melperone) were conducted across a wide dose range in double-blind, placebo-controlled trials. Haloperidol and fluphenazine caused dystonia, and clozapine did not. Remoxipride and melperone also produced dystonia, but remoxipride only did so at doses that were higher than needed for antipsychotic efficacy. Melperone produced dystonia in doses that are in the antipsychotic dose range. The clinical relevance of the findings is discussed.
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PMID:Extrapyramidal syndromes in nonhuman primates: typical and atypical neuroleptics. 167 73

Of 125 patients with neuroleptic (dopamine blocking) drug-induced movement disorders who had been referred to a specialized clinic to differentiate the predominant movement disorder, 63% had tardive dyskinesia, 30% had parkinsonism, 24% had dystonia, 7% had akathisia, and 2% had isolated tremor. Two or more movement disorders coexisted in 31 patients (25%). Functional disability was more severe in patients with akathisia than in other patients. Women outnumbered men at a ratio of 4:1, except for tardive dystonia which affected both sexes equally. The average at onset was 56 years (range, 13 to 87); 69 patients (55%) had onset of movement disorder in the sixth decade. While tardive dystonia was distributed relatively evenly in all age groups, almost a third of patients with parkinsonism had it in the eighth decade. Haloperidol was implicated in 47 patients (37%), followed by amitriptyline/perphenazine in 30%, thioridazine in 27%, and chlorpromazine in 20%. Metoclopramide-induced movement disorders were found in 10 (8%). Most patients (101 or 81%) had history of psychiatric illnesses, but of these only 44 had psychosis. Neuroleptic drugs had been prescribed for 33 patients (26%) who had gastrointestinal problems. It is important to recognize and differentiate various drug-induced movement disorders because such differentiation has pathophysiologic and therapeutic implications. Many patients could have been treated with less potent drugs.
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PMID:Neurologic approach to drug-induced movement disorders: a study of 125 patients. 197 59

Haloperidol exhibits a high affinity for a subclass of sigma- "opiate" binding sites which have a unique anatomic distribution and a unique drug selectivity pattern. These binding sites differ from phencyclidine-sensitive sigma-receptors and are found in many brain areas involved in the control of movement. 1,3-Di-o-tolylguanidine (DTG), a highly selective ligand for the haloperidol-sensitive sigma-receptor, produced marked dystonia in rats after microinjection into the red nucleus, a motor area rich in this receptor. Haloperidol and another sigma-ligand [(+)-SKF 10,047] produced similar effects. On the other hand, clozapine, an antipsychotic drug which fails to bind to sigma-receptors and fails to induce movement disorders in humans, failed to induce these dystonic reactions in rats. Phencyclidine was also without effect, as were injections of the active compounds in sites distant to the red nucleus. Microinjections of DTG in the substantia nigra produced vigorous contralateral circling behavior at extremely low doses. These findings suggest that sigma-binding sites represent biologically functional receptors that are active in the neural control of movement. Since haloperidol (and many other antipsychotic drugs) exhibit an affinity for sigma-receptors which is at least equal to its affinity for dopamine receptors, these data raise the further possibility that sigma-receptors are involved in the motor side effects of antipsychotic drugs.
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PMID:Evidence for a role of haloperidol-sensitive sigma-'opiate' receptors in the motor effects of antipsychotic drugs. 289 93

Haloperidol induced catalepsy with a continuous dose-response between 0 or 0.03 and 10 mg/kg, IP in Brown Norway (BN), Fischer (FR). Long-Evans (LE), and Sprague-Dawley (SD) rats, with similar ED50 values for males (0.23-0.42 mg/kg), and generally greater but more varied drug sensitivity in females (ED50 = 0.13-0.45 mg/kg). Inconsistent findings regarding a biphasic dose-effect relationship in SD male and LE female rats led to testing both sexes and strains up to 200 mg/kg. Females showed a greater tendency than males of both strains to yield lower catalepsy scores at doses greater than 10 mg/kg, but in association with gross neurological toxicity. This paradigm evidently is not an adequate model for a proposed biphasic relationship between doses of high potency neuroleptic agents and acute dystonia in man.
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PMID:Dose-catalepsy response to haloperidol in rat: effects of strain and sex. 320 87

Haloperidol was administered to 12 subjects intravenously (0.125 mg/kg) and to nine subjects orally (0.5 mg/kg). These doses produced sedation in most subjects. A minimal decrease in orthostatic blood pressure was observed. Administration of the Profile of Mood States to these subjects revealed effects on factor 4, vigor-activity, and factor 6, confusion-bewilderment, but many subjects could not complete testing due to excessive sedation. Haloperidol concentrations were obtained during testing and correlated moderately with scores of these subscales. Correlation was also noted between haloperidol concentration and chlorpromazine effect as measured by the Addiction Research Center Inventory. Extrapyramidal reactions, mainly acute dystonic reactions and akathisia, were common. Dystonia occurred in four subjects after intravenous, and three subjects, after oral administration. Akathisia occurred in eight subjects after intravenous, and three subjects after oral administration. Extrapyramidal reactions tended to occur relatively early or relatively late, at times when drug concentrations were far less than peak values.
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PMID:Mood alteration following oral and intravenous haloperidol and relationship to drug concentration in normal subjects. 400 74

The effects of serotonin (5-hydroxytryptamine; 5-HT) antagonists and 5-HT uptake inhibitors on the behavioral response to amphetamine and haloperidol in monkeys (cercopithecus aethiops) were investigated. Amphetamine increased locomotor activity and reactivity and induced repetitive movements of head, limbs and trunk, but no oral hyperkinesia. Haloperidol induced dystonia and parkinsonism. Pretreatment with the 5-HT antagonists cyproheptadine and mianserin increased amphetamine-induced locomotor activity, reactivity and repetitive movements and decreased haloperidol-induced dystonia and parkinsonism. Conversely the 5-HT uptake inhibitors paroxetine and CGP 6085 A decreased amphetamine-induced repetitive movements and aggravated haloperidol-induced dystonia and parkinsonism. The 5-HT uptake inhibitors produced oral hyperkinesia resembling human tardive dyskinesia, which was intensified by amphetamine and blocked by haloperidol. These findings support the suggestion that 5-HT inhibits dopamine functions and may imply that 5-HT antagonists could have a beneficial effect against acute extrapyramidal side-effects of neuroleptic treatment. 5-HT uptake inhibitors in the monkey may serve as a model for tardive dyskinesia.
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PMID:Behavioral aspects of serotonin-dopamine interaction in the monkey. 408 56

The effects of the atypical neuroleptic clozapine were studied in an inbred line of Syrian golden hamsters with generalized dystonia, i.e. a frequent movement disorder in humans. The effects of clozapine were compared with those of the classical neuroleptic, haloperidol. Clozapine, 7.5-20 mg/kg i.p., potently reduced the severity of dystonic attacks in the mutant hamster model, but induced marked sedation at these doses. Lower doses were ineffective. Haloperidol, 0.5 mg/kg i.p., significantly reduced the severity of dystonia without marked sedation. The finding that clozapine possesses antidystonic potency similar to that of haloperidol in a genetic model of dystonia might suggest that this atypical neuroleptic is an effective alternative in the treatment of dystonic patients who respond to neuroleptics, particularly because of the clinical evidence that clozapine is almost devoid of extrapyramidal adverse effects.
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PMID:The atypical neuroleptic, clozapine, exerts antidystonic activity in a mutant hamster model. Comparison with haloperidol. 828 96

The effects of chronic treatment for 28 days with the oral D1 (NNC 22-0215) or D2 (haloperidol) antagonist were evaluated in nonhuman primates in a double blind, placebo controlled crossover trial. Cebus monkeys, 10-18 years old, which were previously sensitized to neuroleptics, were treated in three different groups with NNC 22-0215 2-3 mg/kg PO (n = 6), haloperidol 2-3 mg/kg PO (n = 5), or lactose placebo (n = 7) each day in a banana slice. At the end of 28 days the NNC 22-0215 group crossed over to haloperidol and the haloperidol group crossed over to NNC 22-0215 for 28 more days. The lactose group continued on lactose. Extrapyramidal symptoms (EPS) of dystonia and sedation were scored daily. Initially both NNC 22-0215 and haloperidol produced equal rates of dystonia. However, the NNC 22-0215 group demonstrated nearly full desensitization by day 2 and showed no EPS by day 6, whereas the haloperidol group had increased EPS during the first week, followed by moderate desensitization to EPS, but continued to have symptoms on each of the 28 days of treatment. At crossover, the previously treated haloperidol group rapidly desensitized with NNC 22-0215 by day 4 to show no EPS, whereas the previously treated NNC 22-0215 group showed full EPS on the first day of haloperidol and had EPS continue over the next 28 days of treatment. Sedation from NNC 22-0215 also desensitized within the first week of treatment. Haloperidol produced minimal sedation that did not change. The profound difference in rates of desensitization between repeated D1 and D2 antagonist treatment suggests that D1 antagonists in the clinic may produce EPS side effects for only the first few days, in contrast to the continuous acute EPS associated with chronic neuroleptic treatment.
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PMID:The effects of D1 (NNC 22-0215) and D2 (haloperidol) antagonists in a chronic double-blind placebo controlled trial in cebus monkeys. 858 8


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