The exact pathophysiologic mechanisms of spasmodic torticollis and other idiopathic torsion dystonias remain largely unknown. Thus, a variety of drugs have been used alone or in combination on an empirical basis to treat these disorders, but to date none have efficacy that is proven and consistent. The drugs in use include anticholinergics, benzodiazepines, dopaminergics and dopamine antagonists with variable degrees of clinical improvement. Botulinum toxin A injection treatment for spasmodic torticollis is safe and efficacious with minimal adverse effect. However, it is expensive and beneficial effects are short-lasting. Only when a spasmodic torticollis patient's symptoms are refractory to combined treatment, using various drugs and Botulinum toxin injections, should the patient be considered a candidate for neurosurgical procedures.
Benzodiazepines/therapeutic use ; Botulinum Toxins/*therapeutic use ; Dopamine Agents/therapeutic use ; Dopamine Antagonists ; Human ; Parasympatholytics/therapeutic use ; Spasm/*drug therapy ; Torticollis/*drug therapy

Parkinson's disease is the second most common neurodegenerative disease in the world. Beta-arrestin-2 has been reported to be an important protein involved in D(2) dopamine receptor desensitization, which is essential to Parkinson's disease. Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson's disease has recently been shown. We studied the interaction between D(2) dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis. The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D(2) dopamine receptor interaction among them. These compounds are promising therapies for Parkinson's disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.
Arrestins ; antagonists & inhibitors ; metabolism ; Dopamine ; metabolism ; Dopamine Antagonists ; therapeutic use ; Dopamine D2 Receptor Antagonists ; Drug Evaluation, Preclinical ; Electrophoresis, Capillary ; Humans ; Parkinson Disease ; drug therapy ; metabolism ; pathology ; Receptors, Dopamine D2 ; metabolism ; Signal Transduction ; beta-Arrestin 2 ; beta-Arrestins

PURPOSE: We investigated what kinds of neurotransmitters are related with electroacupuncture (EA) analgesia in an arthritic pain model of rats. MATERIALS AND METHODS: One hundred rats were assigned to six groups: control, EA, opioid, adrenergic, serotonin and dopamine group. A standardized model of inflammatory arthritis was produced by injecting 2% carrageenan into the knee joint cavity. EA was applied to an acupoint for 30 min in all groups except fo the control group. In the opioid, adrenergic, serotonin and dopamine groups, each receptor antagonist was injected intraperitoneally to their respective group before initiating EA. RESULTS: In the opioid receptor antagonist group, adrenergic receptor antagonist group, serotonin receptor antagonist group, dopamine receptor antagonist group and the control group weight-bearing force decreased significantly from 30 min to 180 min after EA in comparison with the EA group. CONCLUSION: The analgesic effects of EA are related to opioid, adrenergic, serotonin and dopamine receptors in an arthritic pain model of rats.
Acupuncture Analgesia/*methods ; Adrenergic Antagonists/therapeutic use ; Animals ; Arthritis/chemically induced/drug therapy/physiopathology/*therapy ; Carrageenan/toxicity ; Dopamine Antagonists/therapeutic use ; Electroacupuncture/*methods ; Male ; Neurotransmitter Agents/*metabolism ; Pain/drug therapy/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic/metabolism ; Receptors, Dopamine/metabolism ; Receptors, Opioid/antagonists & inhibitors/metabolism ; Receptors, Serotonin/metabolism ; Serotonin Antagonists/therapeutic use

Adenoma ; complications ; pathology ; Adult ; Antipsychotic Agents ; adverse effects ; therapeutic use ; Aripiprazole ; Benzodiazepines ; adverse effects ; therapeutic use ; Bromocriptine ; adverse effects ; therapeutic use ; Dopamine Antagonists ; adverse effects ; therapeutic use ; Female ; Hormone Antagonists ; adverse effects ; therapeutic use ; Humans ; Hyperprolactinemia ; complications ; etiology ; Piperazines ; adverse effects ; therapeutic use ; Pituitary Neoplasms ; complications ; pathology ; Quinolones ; adverse effects ; therapeutic use ; Risperidone ; adverse effects ; therapeutic use ; Schizophrenia ; drug therapy ; etiology ; pathology ; Serotonin Antagonists ; adverse effects ; therapeutic use ; Trifluoperazine ; adverse effects ; therapeutic use

BACKGROUND/AIMS: It is unknown whether the prokinetics improve the quality of life in patients with functional dyspepsia. Thus, we evaluate the effect of the mosapride, selective 5-HT4 agonist, on the symptom and life quality of patients with functional dyspepsia using the Nepean dyspepsia index-Korean version (NDI-K), a reliable and validated disease-specific quality of life questionnaire. METHODS: A single, open trial was performed in 129 patients with functional dyspepsia. Patients were received mosapride 5 mg t.i.d before each meal for 4 weeks. The symptoms and quality of life were measured with the NDI-K at baseline and 4 weeks. The responsiveness of the NDI-K was evaluated by correlation with symptom scores. RESULTS: All the 15 symptom scores and the dyspepsia score decreased after treatment (p<0.05). The total symptom score decreased from 60.9 +/- 25.8 to 24.7 +/- 20.4 (p=0.001). Correlations were observed between the total symptom score and the NDI-K score (r=0.47, p=0.001), and between the total symptom score and each score in 5 subscales (r=0.25-0.44, p=0.001). The NDI-K score was significantly increased in the effective group whose dyspepsia score decreased more than 50% of the score at baseline, compared with that of ineffective group. Any significant adverse effect and prolongation of QT interval were not occurred in all patients. CONCLUSIONS: A prokinetic drug, mosapride improves the symptoms and the quality of life in patients with functional dyspepsia.
Adult ; Aged ; Benzamides/*therapeutic use ; Dopamine Antagonists/*therapeutic use ; Dyspepsia/diagnosis/*drug therapy ; English Abstract ; Female ; Gastrointestinal Agents/*therapeutic use ; Humans ; Male ; Middle Aged ; Morpholines/*therapeutic use ; *Quality of Life ; Questionnaires

OBJECTIVETo observe the long-term changes in anxiety-like behavior and tyrosine hydroxylase (TH) expression in the substantia nigra (SN) after hypoxic-ischemic brain damage (HIBD) in a neonatal rat model and to further explore the relationship between dopamine (DA) level and long-term anxiety-like behavior using the DA receptor (DAR) antagonist.

METHODSSeven-day-old (P7) neonatal Sprague-Dawley (SD) rats were randomized into normal control, sham-operated, HIBD and HIBD+DAR antagonist groups. HIBD model was prepared by ligating the right common carotid artery and 8% hypoxia exposure. The rats in the sham-operated group were sham-operated and were not subjected to right common carotid artery ligation and hypoxia exposure. The DAR antagonist was injected intraperitoneally before and after inducing HIBD. The same amount of normal saline was given to the other three groups as a control. Anxiety-like behavior was evaluated by elevated plus maze test, and TH expression in the SN was measured by immunohistochemistry on P14, P21, and P28.

RESULTSOn P21 and P28, the time spent in the open arms and the percentage of open arms entries in the HIBD group were significantly increased compared with those in the normal control, sham-operated and HIBD+DAR antagonist groups (P<0.05); in addition, the HIBD+DAR antagonist group showed a significantly longer time spent in the open arms than the normal control group (P<0.05). On P14, P21, and P28, TH expression in the HIBD and HIBD+DAR antagonist groups was significantly lower than that in the normal control and sham-operated groups, and TH level in the HIBD group was significantly lower than that in the HIBD+DAR antagonist group (P<0.05).

CONCLUSIONSDAR antagonist allows the restoration of anxiety-like behavior and alleviates the damage to dopaminergic neurons in SD rats after HIBD.

Animals ; Animals, Newborn ; Anxiety ; etiology ; prevention & control ; Dopamine Antagonists ; therapeutic use ; Hypoxia-Ischemia, Brain ; complications ; Maze Learning ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine ; physiology ; Substantia Nigra ; enzymology ; Tyrosine 3-Monooxygenase ; analysis

The aim of this study was to investigate the outcome, and optimal duration of medical treatment in children with superior mesenteric artery syndrome (SMAS). Eighteen children with SMAS were retrospectively studied. The data reviewed included demographics, presenting symptoms, co-morbid conditions, clinical courses, nutritional status, treatments, and outcomes. The three most common symptoms were postprandial discomfort (67.7%), abdominal pain (61.1%), and early satiety (50%). The median duration of symptoms before diagnosis was 68 days. The most common co-morbid condition was weight loss (50%), followed by growth spurt (22.2%) and bile reflux gastropathy (16.7%). Body mass index (BMI) was normal in 72.2% of the patients. Medical management was successful in 13 patients (72.2%). The median duration of treatment was 45 days. Nine patients (50%) had good outcomes without recurrence, 5 patients (27.8%) had moderate outcomes, and 4 patients (22.2%) had poor outcomes. A time limit of >6 weeks for the duration of medical management tended to be associated with worse outcomes (P=0.018). SMAS often developed in patients with normal BMI or no weight loss. Medical treatment has a high success rate, and children with SMAS should be treated medically for at least 6 weeks before surgical treatment is considered.
Adolescent ; Bile Reflux/diagnosis ; Child ; Child, Preschool ; Demography ; Domperidone/therapeutic use ; Dopamine Antagonists/therapeutic use ; Drug Administration Schedule ; Female ; Histamine H2 Antagonists/therapeutic use ; Humans ; Infant ; Male ; Parenteral Nutrition ; Retrospective Studies ; Superior Mesenteric Artery Syndrome/*diagnosis/drug therapy ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome ; Weight Loss

OBJECTIVENeuroinflammation with microglial activation has been implicated to have a strong association with the progressive dopaminergic neuronal loss in Parkinson's disease (PD). The present study was undertaken to evaluate the activation profile of microglia in 1-methyl-4-phenyl pyridinium (MPP+)-induced hemiparkinsonian rats. Triptolide, a potent immunosuppressant and microglia inhibitor, was then examined for its efficacy in protecting dopaminergic neurons from injury and ameliorating behavioral disabilities induced by MPP+.

METHODSThe rat model of PD was established by intranigral microinjection of MPP+. At baseline and on day 1, 3, 7, 14, 21 following MPP+ injection, the degree of microglial activation was examined by detecting the immunodensity of OX-42 (microglia marker) in the substantia nigra (SN). The number of viable dopaminergic neurons was determined by measuring tyrosine hydroxylase (TH) positive neurons in the SN. Behavioral performances were evaluated by counting the number of rotations induced by apomorphine, calculating scores of forelimb akinesia and vibrissae-elicited forelimb placing asymmetry.

RESULTSIntranigral injection of MPP+ resulted in robust activation of microglia, progressive depletion of dopaminergic neurons, and ongoing aggravation of behavioral disabilities in rats. Triptolide significantly inhibited microglial activation, partially prevented dopaminergic cells from death and improved behavioral performances.

CONCLUSIONThese data demonstrated for the first time a neuroprotective effect of triptolide on dopaminergic neurons in MPP+-induced hemiparkinsonian rats. The protective effect of triptolide may, at least partially, be related to the inhibition of MPP+-induced microglial activation. Our results lend strong support to the use of immunosuppressive agents in the management of PD.

1-Methyl-4-phenylpyridinium ; antagonists & inhibitors ; toxicity ; Animals ; Biomarkers ; metabolism ; CD11b Antigen ; analysis ; metabolism ; Cell Count ; Cell Survival ; drug effects ; physiology ; Disability Evaluation ; Diterpenes ; pharmacology ; therapeutic use ; Dopamine ; metabolism ; Encephalitis ; drug therapy ; immunology ; prevention & control ; Epoxy Compounds ; pharmacology ; therapeutic use ; Gliosis ; drug therapy ; immunology ; prevention & control ; Herbicides ; antagonists & inhibitors ; toxicity ; Immunosuppression ; methods ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Male ; Microglia ; drug effects ; immunology ; Neurons ; drug effects ; immunology ; pathology ; Parkinsonian Disorders ; drug therapy ; immunology ; physiopathology ; Phenanthrenes ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; immunology ; physiopathology ; Treatment Outcome ; Tyrosine 3-Monooxygenase ; analysis ; metabolism