Harris P Q, Brown S J, Friedman M J, Bacopoulos N G
Biol Psychiatry. 1984 Jun;19(6):849-60.
Plasma neuroleptic and homovanillic acid (HVA) levels are reported for a group of psychotic subjects exhibiting clinical improvement in response to neuroleptic medication. Clinically effective plasma neuroleptic levels, measured by a radioreceptor assay and expressed as either nanomolar concentration of parent drug or as haloperidol equivalents, were different for the seven neuroleptics tested. Plasma HVA, measured by high-pressure liquid chromatography with electrochemical detection (LCEC), increased in response to initiation of neuroleptic treatment and decreased when neuroleptic medication was withdrawn. No correlations were found between plasma neuroleptic level and HVA level or between HVA level and clinical response. Mean therapeutic plasma levels of neuroleptics, expressed as nanomolar concentration of parent drug, correlated with the potencies of the same drug in displacing 3H-dopamine from D-1 and D-2 receptors in rat striatal membranes. This represents the first report that clinically measured plasma concentrations are high enough to displace dopamine from its specific receptors in the CNS.
报告了一组精神病患者在接受抗精神病药物治疗后临床症状改善时的血浆抗精神病药物和高香草酸（HVA）水平。通过放射受体测定法测量并以母体药物的纳摩尔浓度或氟哌啶醇等效物表示的临床有效血浆抗精神病药物水平，对于所测试的七种抗精神病药物而言是不同的。通过高压液相色谱-电化学检测（LCEC）测量的血浆HVA，在开始抗精神病药物治疗时升高，而在停用抗精神病药物时降低。未发现血浆抗精神病药物水平与HVA水平之间或HVA水平与临床反应之间存在相关性。以母体药物的纳摩尔浓度表示的抗精神病药物的平均治疗血浆水平，与同一药物在大鼠纹状体膜中从D-1和D-2受体置换3H-多巴胺的效力相关。这是首次报道临床测量的血浆浓度高到足以在中枢神经系统中从其特定受体置换多巴胺。
