Scheinin M, Syvälahti E K, Hietala J, Huupponen R, Pihlajamäki K, Seppälä O P, Säkö E
Prog Neuropsychopharmacol Biol Psychiatry. 1985;9(4):441-9. doi: 10.1016/0278-5846(85)90198-8.
Two doses of apomorphine (0.005 mg/kg as a subcutaneous injection and 0.015 mg/kg as a 90 min i.v. infusion), and corresponding placebo treatments, were administered to 11 chronic medicated schizophrenic patients and to 8 healthy control subjects. The purpose of the study was to asses the usefulness of drug-induced alterations in the concentration of homovanillic acid (HVA) in plasma as indicators of dopamine autoreceptor sensitivity in the central nervous system. Growth hormone and prolactin in serum were also measured and used as indicators of postsynaptic dopaminergic drug effects. In the control subjects, i.v. apomorphine increased growth hormone in serum from 1.8 +/- 0.2 to 28.3 +/- 4.6 ng/ml and reduced prolactin by 57 +/- 7%. In the patients, apomorphine caused only weak neuroendocrine effects. HVA in plasma was not affected by apomorphine in either group of subjects. The results for growth hormone and prolactin indicate that postsynaptic dopamine receptors in the tubero-infundibular system are antagonized to a considerable degree also during chronic treatment with neuroleptics. The lack of effect of apomorphine on HVA levels suggests that HVA in plasma is not a sensitive indicator of the inhibition of dopamine release caused by small doses of apomorphine and mediated through dopamine auto-receptors. Supersensitivity of this class of receptors could not be demonstrated in our patients, which contrasts with some earlier results.
给11名慢性药物治疗的精神分裂症患者和8名健康对照者分别注射两剂阿扑吗啡(皮下注射剂量为0.005mg/kg,静脉输注90分钟剂量为0.015mg/kg)以及相应的安慰剂。本研究的目的是评估药物诱导的血浆中高香草酸(HVA)浓度变化作为中枢神经系统多巴胺自身受体敏感性指标的有效性。同时还测量了血清中的生长激素和催乳素,并将其用作突触后多巴胺能药物作用的指标。在对照者中,静脉注射阿扑吗啡使血清生长激素从1.8±0.2ng/ml增加到28.3±4.6ng/ml,催乳素降低了57±7%。在患者中,阿扑吗啡仅产生微弱的神经内分泌效应。两组受试者的血浆HVA均不受阿扑吗啡影响。生长激素和催乳素的结果表明,在使用抗精神病药物进行慢性治疗期间,结节-漏斗系统中的突触后多巴胺受体也受到相当程度的拮抗。阿扑吗啡对HVA水平无影响,这表明血浆中的HVA不是小剂量阿扑吗啡通过多巴胺自身受体介导的多巴胺释放抑制的敏感指标。在我们的患者中未能证明这类受体的超敏反应,这与一些早期结果形成对比。