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)

In 4 out of 11 cebus apella monkeys given haloperidol (0.05 - 1.0 mg/kg/d) orally for up to 35 months signs of tardive dyskinesia (TD) hav developed: 1) One monkey developed barely noticeable TD after 4 months, but showed marked and increasing symtpoms of both generalized choreic and buccolingual TD after 8 months. This animal died 3 months after discontinuation of haloperidol. At that time the signs of TD were still prominent. 2) In one monkey bucco-lingual TD appeared after 3 months and was still reversible on discontinuation of haloperidol at 5 months. After a further 12 months of haloperidol, the TD signs proved to be long lasting, possibly irreversible, in this animal. 3) A third monkey showed slight and transient signs of TD at 14 months, but following a further 20 months af haloperidol administration a choreiform syndrome became porminent after drug withdrawal. 4) After 34 months a similar syndrome of choreic movements has been noticed in another animal, increasing after withdrawal of haloperidol. The other 7 monkeys have received haloperidol for 3 - 15 months, without developing any signs of TD. Attacks of acute dystonia have been noticed in all animals, sometimes necessitating anticholinergic medication or decreases in the daily haloperidol dose.
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PMID:Development of acute dystonia and tardive dyskinesia in cebus monkeys. 11 74

Cebus apella monkeys subjected to chronic haloperidol administration develop neurologic disturbances very similar to neuroleptic-induced acute dystonia human beings. After varying lengths of time, certain monkeys develop a prolonged dyskinetic syndrome resembling tardive dyskinesia (TD), as seen clinically. Two monkeys with signs of TD were given single intramuscular injections of various compounds with known effects on the catecholaminergic, cholinergic, serotoninergic and GABA-ergic neurotransmittor systems, and their effect on the TD signs were rated. Dopamine receptor blockers as well as cholinergics had an ameliorating effect on the symptoms. Some compounds known to activate the GABA system, including some benzodiazepines and the GABA-transaminase inhibitor amino-oxyacetic acid, also reduced the symptoms, as did the serotonin precursor L-5HTP. Results with serotonin antagonists were equivocal. It is concluded that dopamine receptor blockade, as well as increased activity within the GABA-ergic or cholinergic systems cause alleviation of TD. The findings are in agreement with earlier reports in man and thus seem to validate this primate model.
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PMID:Pharmacological modification of experimental tardive dyskinesia. 11 27

This review covers recent advances in a variety of dyskinesias. Introduction of new drugs for the treatment of myoclonus and sensory biofeedback therapy for focal dystonia are expanding our concepts of these types of movement disorders. Progress in the treatment of action myoclonus is especially noteworthy and has led to the implication of serotonin deficit in the pathophysiology of this syndrome. Knowledge of the biochemical pathology of Huntington's chorea has outpaced therapy for this disorder, but new forms of therapy have been proposed based on the chemical findings. Basic pharmacologic studies suggest pathophysiologic mechanisms for the syndrome known as tardive dyskinesia, but treatment is still far from ideal for this disorder. Other movement disorders with recent therapeutic advances include essential tremor and hemiballism. This review will cover only those dyskinesias in which new therapies have been advanced in the last few years. Aside from parkinsonism, which will not be discussed here, progress in the treatment of movement disorders has been slow, but steady. New drugs are being tested constantly, and the purpose of this review is to call attention to the ongoing evaluation in this field. Descriptions and etiologies for these dyskinesias are covered elsewhere (Fahn, 1976a) and therefore are not repeated here.
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PMID:New approaches in the management of hyperkinetic movement disorders. 30 60

A dopamine agonist (apomorphine) and a cholinomimetic drug (physostigmine) were administered to five patients with blepharospasm and oromandibular dystonia (Meige disease). The effects of haloperidol and levodopa were also assessed. Apomorphine lessened and physostigmine aggravated the facial dyskinesias in all patients, while placebo injections had no consistent effect. Levodopa did not modify the symptoms, but haloperidol attentuated the facial dystonia. Dysfunction of the basal ganglia, characterized by a state of striatal dopamine preponderance, probably underlies the dystonic spasms in Meige disease. The prominent cholinergic enhancement of facial dyskinesias may distinguish this disorder pharmacologically from tardive dyskinesia, a differentiation which has practical therapeutic implications.
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PMID:Meige disease: striatal dopaminergic preponderance. 37 89

The authors describe two cases of tardive dyskinesia in which severe axial dystonia and intense facial grimacing produced marked discomfort as well as social and physical disability. Both patients experienced the onset of psychiatric symptoms as young adults, showed a prompt response to antipsychotic drug therapy, and were subsequently left on maintenance treatment for indefinite periods. The severity of this frequently irreversible and disabling condition warrants careful consideration in the use of long-term antipsychotic drug treatment in the young psychiatric outpatient population.
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PMID:Tardive dyskinesia in young adults. 40 2

In three cebus monkeys the chronic daily administration of haloperidol (0.5 mg/kg/day orally) created sedation and parkinsonism during the first 5-7 weeks. Later the animals developed signs reminiscent of acute dystonia, as seen in the clinic during treatment with neuroleptics. These signs were dose-dependent and in extreme cases included widespread tonic and clonic seizures. After 3 and 12 months, respectively, two of the cebus monkeys developed buccolingual signs (grimacing and tongue protrusion), similar to tardive dyskinesia in the clinic. The tardive dyskinesia symptoms were reduced in a dose-dependent manner after each haloperidol administration, being most pronounced in the morning before haloperidol was given. Biperiden reduced acute dystonia but reinstated signs of tardive dyskinesia, which had been abolished by haloperidol. It is suggested that cebus monkeys may provide a useful animal model for the study of neurologic long-term complications from neuroleptic drugs.
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PMID:Haloperidol-induced tardive dyskinesia in monkeys. 82 68

Animal data indicate that serotonin (5-HT) is a major neurotransmitter involved in the control of numerous central nervous system functions including mood, aggression, pain, anxiety, sleep, memory, eating behavior, addictive behavior, temperature control, endocrine regulation, and motor behavior. Moreover, there is evidence that abnormalities of 5-HT functions are related to the pathophysiology of diverse neurological conditions including Parkinson's disease, tardive dyskinesia, akathisia, dystonia, Huntington's disease, familial tremor, restless legs syndrome, myoclonus, Gilles de la Tourette's syndrome, multiple sclerosis, sleep disorders, and dementia. The psychiatric disorders of schizophrenia, mania, depression, aggressive and self-injurious behavior, obsessive compulsive disorder, seasonal affective disorder, substance abuse, hypersexuality, anxiety disorders, bulimia, childhood hyperactivity, and behavioral disorders in geriatric patients have been linked to impaired central 5-HT functions. Tryptophan, the natural amino acid precursor in 5-HT biosynthesis, increases 5-HT synthesis in the brain and, therefore, may stimulate 5-HT release and function. Since it is a natural constituent of the diet, tryptophan should have low toxicity and produce few side effects. Based on these advantages, dietary tryptophan supplementation has been used in the management of neuropsychiatric disorders with variable success. This review summarizes current clinical use of tryptophan supplementation in neuropsychiatric disorders.
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PMID:L-tryptophan in neuropsychiatric disorders: a review. 130 30

One of the main advantages of clozapine is that it rarely produces extrapyramidal syndromes and tardive dyskinesia. This advantage is linked to the atypical biochemical profile of clozapine, especially its combined and low blockade of D1 and D2 receptors. The level of D2 receptor blockade is too low to induce extrapyramidal side-effects, and D1 antagonists have a lower extrapyramidal side-effect potential than traditional D2 neuroleptics, especially with respect to dystonia. The combined and balanced D1/D2 receptor blockade may prevent the development of a dysbalance between D1/D2 receptor function (in favour of D1) which otherwise might lead to tardive dyskinesia.
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PMID:Clozapine and D1/D2 antagonism in extrapyramidal functions. 141 86

On the basis of the association of negative schizophrenia with parkinsonism and early age of onset, we predicted that the latter two would covary, as reflecting a similar pathological process. To test this prediction, we studied in 40 neuroleptic-treated female schizophrenic patients with drug-induced movement disorders the association of age at onset with drug-induced parkinsonism and, for comparison, also with persistent tardive dyskinesia (TD) and acute drug-induced dystonia. We found that onset of schizophrenia during adolescence, significantly predicted the presence of parkinsonism but, by contrast, was unrelated to TD and acute drug-induced dystonia. Our findings suggest a specific association between early age at onset of schizophrenia and parkinsonism, implying that the former may be a risk factor for parkinsonism. The significance of these findings to the pathophysiology of negative schizophrenia and parkinsonism are discussed.
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PMID:Drug-induced parkinsonism: relationship to age at onset of schizophrenia. 168 Jul 77

The literature on the pharmacologic treatment of schizophrenia and schizoaffective disorders is reviewed (116 references). All clinically active antipsychotic drugs share the ability to block postsynaptic dopamine receptors in the central nervous system. Their potencies vary, chlorpromazine and thioridazine being the least potent and fluphenazine and haloperidol the most potent. The adverse effects of the neuroleptics include acute dystonia, parkinsonian symptoms (extrapyramidal symptoms), akathisia, tardive dyskinesia, and tardive dystonia. When used at equipotent doses, all classic neuroleptics now available are equally effective in the treatment of schizophrenia. Choice of drug is based on adverse effects and patient response. The neuroleptics are effective in most acute exacerbations of schizophrenia and for the prevention or mitigation of relapse. Their effects are more pronounced on the positive symptoms of schizophrenia, such as hallucinations, delusions, disordered thinking, and paranoia, than on the negative symptoms, such as deficits in social interaction, emotional expression, and motivation. Strategies for acute and maintenance treatment and for the management of treatment-resistant patients are reviewed. The pharmacology and clinical use of the newer atypical neuroleptics, particularly clozapine, and their adverse effects are discussed.
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PMID:Pharmacologic treatment of schizophrenia. 168 69


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