POSITRON EMISSION TOMOGRAPHY STUDIES ON D-2 AND 5-HT2 RECEPTOR-BINDING IN RISPERIDONE-TREATED SCHIZOPHRENIC-PATIENTS

被引：139

作者：

FARDE, L ^{[1
]}

NYBERG, S ^{[1
]}

OXENSTIERNA, G ^{[1
]}

NAKASHIMA, Y ^{[1
]}

HALLDIN, C ^{[1
]}

ERICSSON, B ^{[1
]}

机构：

[1] JANSSEN PHARMA AB,STOCKHOLM,SWEDEN

来源：

JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY | 1995年 / 15卷 / 01期

关键词：

D O I：

10.1097/00004714-199502001-00004

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

By the use of positron emission tomography (PET), high central dopamine D-2 receptor occupancy (70 to 90%) has been demonstrated in patients treated with conventional neuroleptics. In patients treated with the atypical antipsychotic clozapine, the D-2 occupancy was low (20 to 67%). The effects of clozapine may thus be mediated by a mechanism distinct from D-2 occupancy, The observation that low doses of clozapine (125 to 175 mg daily) induced more than 80% (5-hydroxytryptamine) 5-HT2 occupancy supports the view that 5-HT2 antagonism may be related to the atypical effects of clozapine. Risperidone is a new antipsychotic drug with high affinity in vitro for both central 5-HT2 and D-2 receptors. In this study, me determined the D-2 and 5-HT2 occupancy induced by clinical treatment with risperidone. Four patients with acute exacerbation of schizophrenia were examined by PET after 4 weeks of treatment with risperidone, 6 mg daily. The D-2 occupancy in the striatum was 75 to 80%. The 5-HT2 occupancy in the neocortex was 78 to 88%. This study confirms that, in patients with schizophrenia, treatment with risperidone induces a high D-2 and 5-HT2 occupancy. Risperidone is, accordingly, a suitable drug for the examination of the clincial benefit of combined serotonin and dopamine antagonism.

引用

页码：S19 / S23

页数：5

共 47 条

[1] Carlsson A., Lindqvist M., Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain, Acta Pharmacol Toxicol, 20, pp. 140-144, (1963)
[2] Van Rossum J.M., The significance of dopamine receptor blockade for the mechanism of action of neuroleptic drugs, Arch Int Pharmacodyn, 160, pp. 492-494, (1966)
[3] Seeman P., Lee T., Chau-Wong M., Wong K., Antipsychotic drug doses and neuroleptic/dopamine receptors, Nature, 261, pp. 717-719, (1976)
[4] Creese I., Burt D.R., Snyder S.H., Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs, Science, 192, pp. 481-483, (1976)
[5] Peroutka S.J., Snyder S.H., Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency, Am J Psychiatry, 137, pp. 1518-1522, (1980)
[6] Farde L., Hall H., Ehrin E., Sedvall G., Quantitative analysis of d2 dopamine receptor binding in the living human brain by pet, Science, 231, pp. 258-261, (1986)
[7] Farde L., Nordstrom A.-L., Wiesel F.-A., Pauli S., Haildin C., Sedvall G., Pet-analysis of central dr and d2-dopamine receptor occupancy in patients treated with classical neuroleptics and cloza pinerelation to extrapyramidal side effects, Arch Gen Psychiatry, 49, pp. 538-544, (1992)
[8] Smith M., Wolf A., Brodie J., Arnett C., Barouche F., Shiue C., Fowler J., Russel J., Macgregor R., Wolkin A., Serial [18f]n-methylspiperone petstudies to measure changes in antipsychotic drug d2 receptor occupancy in schizophrenic patients, Biol Psychiatry, 23, pp. 653-663, (1988)
[9] Baron J.C., Martinot J.L., Cambon H., Boulenger J.P., Poirier M.F., Caillard V., Blin J., Huret J.D., Loc'H C., Maziere B., Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment. Correlative evaluation by positron emission tomography and plasma prolactin levels, Psychopharmacology, 99, pp. 463-472, (1989)
[10] Svensson T., Mathe J., Andersson J., Nomikos G., Hildebrand B., Marcus M., Mode of action of atypical neuroleptics in relation to the phencyclidine model of schizophrenia: Role of 5-ht2 and α1-receptor antagonism, J Clin Psychopharmacol, 15, pp. 32S-39S, (1995)

← 1 2 3 4 5 →