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  • 1
    Electronic Resource
    Electronic Resource
    Allelic association between a Ser-9-Gly polymorphism in the dopamine D3 receptor gene and schizophrenia (1996)
    Springer
    Human genetics 〈Berlin〉 97 (1996), S. 714-719 
    Details
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We examined a Ser-9-Gly polymorphism in the dopamine D3 receptor gene for allelic association with schizophrenia in 133 patients currently treated with clozapine and 109 controls. Allele 1 (Ser-9) was significantly more frequent in the patients (69%) than in the controls (56%) (P = 0.004). The 1-1 genotype was more common (43% vs 30%) and the 2-2 genotype less common (5% vs 18%) in patients than in controls. When the patient group was subdivided on the basis of clinical response to clozapine, using a 20-point improvement in the global assessment scale as cut-off, genotype 1-1 was found to be more frequent among the non-responders (53% vs 36%,P = 0.04). To place our results in the context of previous studies of this polymorphism and schizophrenia, we performed a meta-analysis of all published data including the present sample. The combined analysis shows evidence for a modest association between genotype 1-1 and schizophrenia (odds ratio 1.25, 95% confidence interval 1.05–1:49,P = 0.01). These results suggest that the Ser-9 allele, or a nearby polymorphism in linkage disequilibrium, results in a small increase in susceptibility to schizophrenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02346178
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of 6-Hydroxydopamine Lesions of the Medial Prefrontal Cortex on Neurotransmitter Systems in Subcortical Sites in the Rat (1980)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 34 (1980), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of lesions of the catecholamine nerve terminals in the medial prefrontal cortex of the rat on neurotransmitter mechanisms within the basal ganglia has been investigated. Bilateral 6-hydroxydopamine lesions were stereotaxically placed in the dopamine-rich (DA) area of the frontal cortex. Animals were pretreated with desmethylimipramine to block the uptake of neurotoxin into noradrenergic (NA) terminals and to make it more selective for DA terminals. The lesion produced a selective reduction of both NA and DA from the medial prefrontal cortex, a result related to falls in tyrosine hydroxylase activity at this site. Lesioned animals showed enhanced DA turnover and utilisation in striatal and limbic regions. There was no change in subcortical tyrosine hydroxylase activity. In addition there were significant falls in other putative neurotransmitters within basal ganglia sites, including 5-hydroxytryptamine and GABA. Decreased activity of the neurotransmitter-synthesizing enzymes glutamate decarboxylase and choline acetyltransferase was also recorded in certain regions of the basal ganglia. The results suggest that frontal cortical catecholamine systems may serve to regulate various neurotransmitter mechanisms in the basal ganglia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1980.tb04625.x
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats (1980)
    [s.l.] : Nature Publishing Group
    Nature 286 (1980), S. 74-77 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Destruction of catecholamine terminals within the area of the medial prefrontal cortex was performed by infusion of 6-hydroxydopamine (6-OHDA) into this site. Male Porton rats (220-250 g) were pretreated with the noradrenergic uptake blocker desmethylimipramine20 (DMI, 25 mg per kg, ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/286074a0
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  • 4
    Electronic Resource
    Electronic Resource
    Dopamine D2 receptor blockade in vivo with the novel antipsychotics risperidone and remoxipride — an123I-IBZM single photon emission tomography (SPET) study (1995)
    Springer
    Psychopharmacology 117 (1995), S. 55-61 
    Details
    ISSN: 1432-2072
    Keywords: Single photon emission tomography ; D2 dopamine receptors ; Atypical antipsychotics ; Risperidone ; Remoxipride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Risperidone and remoxipride are recently introduced atypical antipsychotics, with clinical efficacy comparable to that of classical antipsychotics but lower propensity to induce extrapyramidal side effects (EPS). It is unclear whether these properties relate to weak dopamine D2 receptor blockade in vivo, as has been suggested for the archetypal atypical antipsychotic clozapine. We have used123I-IBZM single photon emission tomography (SPET) to characterize the patterns of striatal D2 receptor binding in vivo in DSMIII-R-diagnosed schizophrenic and schizo-affective patients treated with either risperidone (n=6) or remoxipride (n=4) but predominantly EPS free. These groups were compared to age- and BPRS- matched subjects from a previously reported D2 receptor binding database of patients treated with clozapine (n=10) and classical antipsychotics (n=10). Patients on risperidone and remoxipride had high levels of D2 receptor blockade, comparable to those of patients on classical antipsychotics, and significantly greater than those obtained with clozapine-treated patients (risperidone versus clozapine,P〈0.005; remoxipride versus clozapine,P〈0.025). These results suggest high levels of striatal D2 receptor occupancy in association with remoxipride and risperidone treatment and argue against modest D2 antagonism as the explanation for the low incidence of EPS associated with these drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245098
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  • 5
    Electronic Resource
    Electronic Resource
    In vivo effects on striatal dopamine D2 receptor binding by the novel atypical antipsychotic drug sertindole – a 123I IBZM single photon emission tomography (SPET) study (1997)
    Springer
    Psychopharmacology 130 (1997), S. 152-158 
    Details
    ISSN: 1432-2072
    Keywords: Key words Sertindole ; Clozapine ; Atypical antipsychotic drugs ; Single photon emission tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The novel antipsychotic drug sertindole has an atypical pharmacological profile. We have estimated striatal D2 dopamine binding in schizophrenic patients treated with sertindole using 123I iodobenzamide (IBZM) SPET. Patients were recruited from a clinical trial of sertindole’s tolerability and efficacy. Striatal D2 binding in sertindole-treated patients (n = 5), was compared with previously reported data from clozapine (n = 10); olanzapine (n = 6); typical antipsychotic responsive (n = 10); and risperidone (n = 6)-treated groups. Mean PANSS (structured clinical interview for the positive and negative syndrome scale) scores showed clinical improvement in the sertindole group. Few extrapyramidal side effects (EPS) were recorded [average Simpson-Angus (SAS) score = 2.6]. Sertindole-treated patients had mean D2 binding indices (± SE) significantly lower than clozapine-treated patients (1.19 ± 0.04) versus (1.49 ± 0.04), and olanzapine-treated patients (1.41 ± 0.06); and similar to those of risperidone (1.24 ± 0.04) and typical antipsychotic responsive (1.25 ± 0.05) treated patients. In this patient sample the preliminary evidence suggests that sertindole’s decreased tendency to induce EPS at clinically therapeutic doses is not due to limited occupancy of striatal D2 receptors in vivo, and as is the case for risperidone, patients are protected from EPS by some other intrinsic effect of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050223
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