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Paradoxical effect of neuroleptic drugs on prolactin secretion by rat pituitary cell cultures

机译:抗精神病药对大鼠垂体细胞分泌催乳素的悖论作用

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Several antipsychotic drugs reverse the dopamine-induced inhibition of prolactin release by rat pituitary cell cultures. Paradoxically, at high doses and without dopamine, antipsychotic drugs can also inhibit prolactin secretion. The mechanism underlying this phenomenon is unclear. Some evidence suggests that these drugs have an agonistic action. We sought to verify whether clozapine and fluphenazine, at doses higher than those reversing dopamine-induced inhibition of prolactin secretion in vitro, show this paradoxical effect and eventually a partial agonistic action. Both antipsychotics inhibited prolactin secretion, clozapine at doses starting from 10~(-6) M and fluphenazine from 10~(-7) M. Haloperidol reversed clozapine-induced prolactin inhibition but left fluphenazine-induced inhibition unchanged. These in vitro findings suggest that clozapine has a partial agonistic action on dopaminergic receptors but fluphenazine does not.
机译:几种抗精神病药可以逆转多巴胺对大鼠垂体细胞培养物催乳素释放的抑制作用。矛盾的是,在没有多巴胺的情况下,高剂量的抗精神病药也可以抑制催乳激素的分泌。这种现象的潜在机制尚不清楚。一些证据表明这些药物具有激动作用。我们试图验证氯氮平和氟奋乃静的剂量是否高于在体外逆转多巴胺诱导的催乳激素分泌抑制的剂量,是否显示出这种矛盾的作用并最终表现出部分激动作用。两种抗精神病药均抑制催乳激素的分泌,氯氮平的剂量从10〜(-6)M开始,氟苯哌嗪的剂量从10〜(-7)M开始。氟哌啶醇可逆转氯氮平诱导的催乳素抑制作用,但氟哌嗪诱导的抑制作用不变。这些体外发现表明,氯氮平对多巴胺能受体具有部分激动作用,而氟奋乃静则没有。

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