In vitro receptor binding and in vivo receptor occupancy in rat and guinea pig brain: risperidone compared with antipsychotic hitherto used
-
- Schotte Alain
- Janssen Research Foundation, Department of Biochemical Pharmacology
-
- Bonaventure Pascal
- Janssen Research Foundation, Department of Biochemical Pharmacology
-
- Janssen Paul F.M.
- Janssen Research Foundation, Department of Biochemical Pharmacology
-
- Leysen Josee E.
- Janssen Research Foundation, Department of Biochemical Pharmacology
書誌事項
- タイトル別名
-
- In Vitro Receptor Binding and In Vivo Receptor Occupancy in Rat and Guinea Pig Brain: Risperidone Compared with Antipsychotics Hitherto Used.
この論文をさがす
抄録
Risperidone was compared with antipsychotics hitherto used for in vitro receptor binding using animal brain or cloned (human) receptors and in vivo receptor occupancy in rat and guinea pig brain following acute treatment. Both in vitro and in vivo, risperidone, 9-OH-risperidone, SM-9018, clozapine and clocapramine showed higher affinity for 5-HT2A- than for D2-receptors, whereas mosapramine, haloperidol, bromperidol and nemonapride had a slight to strong preference for D2- compared to 5-HT2A-receptors. In vivo, risperidone showed the highest potency for 5-HT2A-receptor occupancy; To obtain the same extent of D2-receptor occupancy, a 19-times higher dosage was required. 9-OH-Risperidone, the principal active metabolite of risperidone, showed a receptor occupancy profile comparable to that of risperidone. No regional selectivity for D2-receptor occupancy in mesolimbic vs nigrostriatal areas was detected for any of the compounds. Risperidone differed from the other compounds by the remarkably shallow slope of its D2-receptor dose-occupancy curve. A greater predominance of 5-HT2A-receptor vs D2-receptor occupancy and a more gradual occupancy of D2A-receptors differentiate risperidone from the other compounds. Both properties probably assist in preventing an extensive blockade of D2-receptors, the cause for extrapyramidal symptoms (EPS). The predominant 5-HT2A-receptor occupancy most likely underlies risperidone''s beneficial effects on the negative symptoms of schizophrenia and an adequately low D2-receptor occupancy adds to the treatment of positive symptoms with a low liability of EPS.
収録刊行物
-
- Jpn.J.Pharmacol.
-
Jpn.J.Pharmacol. 69 (4), 399-412, 1995
公益社団法人 日本薬理学会
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1390282679264076288
-
- NII論文ID
- 10006063907
-
- NII書誌ID
- AA00691188
-
- COI
- 1:CAS:528:DyaK28XlslWl
-
- ISSN
- 13473506
- 00215198
-
- PubMed
- 8786644
-
- 本文言語コード
- en
-
- データソース種別
-
- JaLC
- Crossref
- PubMed
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可