Search results for "Basal Ganglia Diseases"

Rotarod impairment: catalepsy-like screening test for antipsychotic side effects.

2009

Extrapyramidal motoric symptoms are casual side effects under antipsychotic medication. New generation antipsychotics are expected to have a reduced risk due to different receptor affinities. Here, haloperidol and the new generation antipsychotics, risperidone, amisulpride, and aripiprazole, were examined with both catalepsy test and rotarod performance test to screen for their usability in mice. Mice treated with haloperidol, risperidone, and aripiprazole showed dose and time-dependent impairment. Amisulpride-treated mice showed no signs of catalepsy. Catalepsy test and rotarod performance test were useful methods to detect side effects of both generation antipsychotics. Catalepsy test pro…

Nitric oxide modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders.

2011

Several recent studies have emphasized a crucial role for the nitrergic system in movement control and the pathophysiology of the basal ganglia (BG). These observations are supported by anatomical evidence demonstrating the presence of nitric oxide synthase (NOS) in all the basal ganglia nuclei. In fact, nitrergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high expression of nitric oxide (NO)-producing neurons, with the striatum having the greatest number, together with important NO afferent input. In this pape…

Mechanism of New Antipsychotic Medications

2003

Antagonism of D 2 -like dopamine receptors is the putative mechanism underlying the antipsychotic efficacy of psychotropic drugs. Positron emission tomographic studies suggest that the antipsychotic effect of dopamine receptor antagonists occurs within a therapeutic window between 60% and 80%(striatal) D 2 receptor occupancy. The incidence of extrapyramidal side effects increases above the 80% threshold. However, the novel atypical antipsychotic drug, aripiprazole, occupies up to 95% of striatal D 2 -like dopamine receptors at clinical doses, and the incidence of extrapyramidal side effects with aripiprazole is no higher than with placebo. The most likely explanation for this finding is ari…

Savoxepine: invalidation of an "atypical" neuroleptic response pattern predicted by animal models in an open clinical trial with schizophrenic patien…

1991

The new tetracyclic compound savoxepine exhibits potent antidopaminergic effects with preferential activity in the hippocampus as compared to striatum in rat brain. As a result of behavioural animal models and regional differences in dopamine receptor binding characteristics, it has been suggested to possess an "atypical" neuroleptic response pattern. In an open clinical trial, savoxepine was administered to 12 in-patients suffering from paranoid schizophrenia and schizophreniform disorder (DSM-III). Eight patients were treated with a stable dose of 0.5 mg per day throughout the study, while in the remaining patients higher doses up to 20 mg/day were administered. Mean total BPRS scores and…

Antipsychotic effects and tolerability of the sigma ligand EMD 57445 (panamesine) and its metabolites in acute schizophrenia: an open clinical trial.

2000

Antipsychotic efficacy and side effects of the selective sigma ligand EMD 57445 (panamesine) were investigated in 12 patients (6 males, 6 females) who met DSM-III-R criteria for schizophrenia. A 4-week open clinical study revealed only modest effects of EMD 57445 and its metabolites on positive and negative symptoms of schizophrenia. Extrapyramidal and other side effects were moderate, although a significant increase in mild dyskinetic movements was found. Five patients, four of whom were females, completed the trial. Dropouts were mainly due to treatment failure. Antipsychotic effects were significantly greater in female than male patients.

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification

2020

International audience; Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromo…

Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis.

2012

Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC.

Overlap between emotional blunting, depression, and extrapyramidal symptoms in schizophrenia

2002

Serotonin Involvement in the Basal Ganglia Pathophysiology: Could the 5-HT2C Receptor be a New Target for Therapeutic Strategies?.

2006

The basal ganglia are a highly interconnected group of subcortical nuclei in the vertebrate brain that play a critical role not only in the control of movements but also in some cognitive and behavioral functions. Several recent studies have emphasized that serotonergic pathways in the central nervous system (CNS) are intimately involved in the modulation of the basal ganglia and in the pathophysiology of human involuntary movement disorders. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of the basal ganglia. In fact, serotonergic terminals have been reported to make synaptic contacts with dopamine (DA)-containing neurons and gamma-amin…

[123I]IBZM SPECT in patients treated with typical and atypical neuroleptics: relationship to drug plasma levels and extrapyramidal side effects

1997

[123I]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor ligand and can be used to visualize brain D2 receptors in humans with single photon emission computerized tomography (SPECT). The ratio of striatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D2 receptor binding in the striatum. Our study sample included six patients treated with haloperidol (3.0-8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscularly), five patients with benperidol (9.0-15.0 mg/day orally) and nine patients treated with clozapine (200.0-600.0 mg/day orally). Typical neuroleptics (TNs) and atypical neuroleptics (ANs) were significantly di…