Kolakowska T, Wiles D H, Gelder M G, McNeilly A S
Psychopharmacology (Berl). 1976 Aug 26;49(1):101-7.
Plasma levels of chlorpromazine (CPZ), 3 of its metabolites and prolactin were measured repeatedly in 18 chronic schizophrenic patients. The patients were studied while on chronic phenothiazine medication (chlorpromazine in 8, other phenothiazines in 10), during 4-6 weeks on placebo and during 6-12 weeks of CPZ treatment. The findings were compared with those obtained during acute CPZ treatment in patients who had received similar CPZ doses but no previous long-term phenothiazine medication. Plasma CPZ levels were similar in the chronic and the acute groups and so was their relation to dose. In neither group was therapeutic effect related to plasma CPZ level. In these chronic patients, in contrast to findings during acute CPZ treatment, neither prolactin level nor the appearance of parkinsonian symptoms was related to plasma drug level. In the chronic group both these effects were less pronounced during the period on CPZ which followed the placebo than were the corresponding effects during CPZ treatment in the acute group. Since plasma CPZ levels of the two groups were similar, these differences may be due to an acquired tolerance of the nervous system to some of the antidopaminergic effects of the drug.
对18例慢性精神分裂症患者反复测量血浆中氯丙嗪（CPZ）及其3种代谢产物和催乳素的水平。在患者接受慢性吩噻嗪类药物治疗时（8例服用氯丙嗪，10例服用其他吩噻嗪类药物）、服用安慰剂4 - 6周期间以及服用氯丙嗪治疗6 - 12周期间对其进行研究。将这些结果与在接受相似氯丙嗪剂量但之前未长期服用吩噻嗪类药物的患者进行急性氯丙嗪治疗期间所获得的结果进行比较。慢性组和急性组的血浆CPZ水平及其与剂量的关系相似。两组的治疗效果均与血浆CPZ水平无关。与急性氯丙嗪治疗期间的结果相反，在这些慢性患者中，催乳素水平和帕金森症状的出现均与血浆药物水平无关。在慢性组中，在服用氯丙嗪期间继安慰剂期之后，这两种效应在程度上均不如急性组氯丙嗪治疗期间相应的效应明显。由于两组的血浆CPZ水平相似，这些差异可能是由于神经系统对该药物的某些抗多巴胺能效应产生了获得性耐受性。
