COMPARISON OF THE PHARMACOLOGICAL CHARACTERISTICS OF [H-3] RACLOPRIDE AND [H-3]SCH 23390 BINDING TO DOPAMINE-RECEPTORS INVIVO IN MOUSE-BRAIN
COMPARISON OF THE PHARMACOLOGICAL CHARACTERISTICS OF [H-3] RACLOPRIDE AND [H-3]SCH 23390 BINDING TO DOPAMINE-RECEPTORS INVIVO IN MOUSE-BRAIN
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DOI：
10.1016/0014-2999(88)90492-x
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发表时间：
1988-01-27
影响因子：
5
通讯作者：
ANDERSEN, PH
中科院分区：
文献类型：
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作者：
ANDERSEN, PH
在小鼠脑中研究了苯甲酰胺衍生物[3 H]雷氯必利的体内结合。该结合是可饱和的、可逆的和立体特异性的。非特异性结合占总结合的5-15%。结合的药理学表征表明多巴胺D2受体的标记，因为结合在体外被对该受体具有高亲和力的化合物强力抑制。另一方面，体外亲和力低的化合物，即，多巴胺D1选择性化合物作为[3 H]雷氯必利结合的抑制剂是弱的或无活性的。[3 H]雷氯必利和[3 H]SCH 23390在体内结合的药理学特征比较表明，具有体外选择性的化合物在体内保留了这种选择性。因此，螺哌利多、氟哌啶醇、l-舒必利、氯波必利、LY 171555和（-）-NPA（（-）-N-丙基-去甲阿扑吗啡）具有D2选择性，而SCH 23390、SKF 38393和SKF 75670具有D1选择性。氯氮平、替洛西平、顺式氟哌噻吨、氯丙嗪和布他洛尔在体内外均为非选择性。然而，与体外相比，一些化合物在体内改变了特征。因此，氟哌拉平和氟奋乃静在体外具有双重D1-D2受体谱，但在体内分别具有D1或D2选择性。培高利特和吗茚酮在体外具有D2选择性，在体内具有D1-D2双重受体特征。总之，[3 H]雷氯必利，在体内，选择性标记多巴胺D2受体。[3 H]雷氯必利和[3 H]SCH 23390在体内结合的药理学特征的比较支持了先前的观察结果，即多巴胺D1受体是各种精神抑制剂的重要靶点，尤其是氯氮平类型。这可能表明多巴胺D1受体的阻断传递抗精神病作用。
In vivo binding of the benzamide derivative [3H]raclopride was studied in mouse brain. The binding was saturable, reversible and stereospecific. Non-specific binding was 5-15% of the total binding. Pharmacological characterization of the binding indicated labelling of dopamine D2 receptors since the binding was potently inhibited by compounds with high affinity for this receptor in vitro. On the other hand, compounds with low affinity in vitro i.e., dopamine D1-selective compounds were weak or inactive as inhibitors of [3H]raclopride binding. A comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding in vivo indicated that compounds with selectivity in vitro retained this selectivity in vivo. Thus, spiroperidol, haloperidol, l-sulpiride, clebopride, LY 171555 and (-)-NPA ((-)-N-propyl-norapomorphine) were D2 selective while SCH 23390, SKF 38393 and SKF 75670 were D1 selective. Clozapine, tilozepine, cis-flupentixol, chlorpromazine and butaclomol were non-selective both in vitro and in vivo. However, a few compounds changed profile in vivo compared to in vitro. Thus, fluperlapine and fluphenazine had a dual D1-D2 receptor profile in vitro but were D1- or D2-selective in vivo, respectively. Pergolide and molindone which were D2-selective in vitro both had a dual D1-D2 receptor profile in vivo. In conclusion, [3H]raclopride, in vivo, selectively labels the dopamine D2 receptor. Comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding in vivo supported the previous observation that the dopamine D1 receptor is an important target for a variety of neuroleptics, especially of the clozapine type. This may indicate that blockade of the dopamine D1 receptor conveys antipsychotic action.