Pigott T A, Hill J L, Grady T A, L'Heureux F, Bernstein S, Rubenstein C S, Murphy D L
Section on Clinical Neuropharmacology, National Institute of Mental Health, Bethesda, MD.
Biol Psychiatry. 1993 Jan 1;33(1):3-14. doi: 10.1016/0006-3223(93)90272-f.
In prior studies form three centers, an exacerbation of obsessive-compulsive disorder (OCD) symptoms was reported in some (55%-83%) patients with OCD receiving the serotonergic agonist m-chlorophenylpiperazine (m-CPP) orally, whereas intravenously administered mCPP produced anxiety but no OCD symptom exacerbation. In the present replication attempt, 27 OCD patients were given mCPP either orally (n = 17) or intravenously (n = 10) under double-blind conditions, using identical behavioral rating measures. OCD symptoms were significantly increased after intravenous mCPP (0.1 mg/kg), but not after oral mCPP (0.5 mg/kg). Anxiety and other ratings were markedly elevated after intravenous mCPP administration. After oral mCPP administration, anxiety and most other self-ratings were only slightly elevated in comparison to placebo administration, and behavioral rating increases were no different for the OCD patients compared to age-matched healthy controls. Pretreatment with the potent serotonin (5-HT) antagonist, metergoline, prior to intravenous mCPP was associated with essentially complete blockade of the exacerbation in OCD symptoms and the other behavioral responses in the OCD patients. These results suggest that the behavioral response of OCD patients to mCPP are variable and depend on the route and dose of mCPP. In addition, the ability of metergoline to antagonize the behavioral effects of intravenous mCPP suggests that these responses are mediated by 5-HT1/5-HT2 receptors.
在先前来自三个中心的研究中，一些（55%-83%）口服血清素能激动剂间氯苯哌嗪（m-CPP）的强迫症（OCD）患者报告了强迫症症状加重，而静脉注射mCPP会引发焦虑，但不会加重强迫症症状。在本次重复试验中，27名强迫症患者在双盲条件下分别口服（n = 17）或静脉注射（n = 10）mCPP，并使用相同的行为评分指标。静脉注射mCPP（0.1 mg/kg）后，强迫症症状显著增加，但口服mCPP（0.5 mg/kg）后未出现这种情况。静脉注射mCPP后，焦虑及其他评分显著升高。口服mCPP后，与服用安慰剂相比，焦虑及大多数其他自评仅略有升高，与年龄匹配的健康对照相比，强迫症患者的行为评分增加并无差异。在静脉注射mCPP之前，先用强效血清素（5-HT）拮抗剂美替拉酮进行预处理，可基本完全阻断强迫症患者的症状加重及其他行为反应。这些结果表明，强迫症患者对mCPP的行为反应存在差异，且取决于mCPP的给药途径和剂量。此外，美替拉酮拮抗静脉注射mCPP行为效应的能力表明，这些反应是由5-HT1/5-HT2受体介导的。
