LIKEABILITY AND DOPAMINE TRANSPORTER OCCUPANCY OF ORAL METHYLPHENIDATE

口服哌醋甲酯的好感度和多巴胺转运蛋白的占有率

• 批准号: 7349589
• 负责人: Thomas J Spencer
• 金额: $ 3.5万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349589
• 关键词: LIKEABILITY; DOPAMINE; TRANSPORTER; OCCUPANCY; ORAL

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The abuse potential of methylphenidate has been related to the drug's capacity to produce a rapid onset of blockade of the presynaptic dopamine transporter in the brain. An oral once-a-day osmotic controlled-release formulation of methylphenidate produces a more gradual rise in plasma methylphenidate concentration, compared with immediate-release methylphenidate. The authors hypothesized that osmotic-release methylphenidate would produce a slower onset of blockade of the presynaptic dopamine transporter and would be associated with a lower risk for detection and likeability, compared to immediate-release methylphenidate. Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Doses predicted to produce equivalent maximum concentration (C(max)) values were selected (40 mg of immediate-release methylphenidate and 90 mg of osmotic-release methylphenidate). Plasma d-methylphenidate levels and responses to detection/likeability questionnaire items were obtained for 10h after methylphenidate administration on two separate occasions. Dopamine transporter receptor occupancies were measured at hours 1, 3, 5, and 7 with a carbon-11-labeled imaging agent (Altropane) and positron emission tomography. Results: Despite similar C(max) values for both formulations, osmotic-release methylphenidate was associated with a longer time to maximum concentration, longer time to maximum CNS dopamine transporter occupancy, and no detection/likeability, compared with immediate-release methylphenidate. Discussion: The findings suggest that the abuse potential of oral methylphenidate is strongly influenced by the rate of delivery and not solely by the magnitude of plasma concentration or brain transporter occupancy. These results advance understanding of the underlying central effects of methylphenidate in humans and identify a potentially less abusable methylphenidate formulation.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。哌醋甲酯的滥用潜力与该药物产生脑突触前多巴胺转运蛋白的封闭的能力有关。与立即释放的甲化酯相比，哌醋甲酯的口服一次渗透控制释放释放制剂的血浆甲基苯甲酯浓度的逐渐增加。作者假设渗透释放甲化酯会产生较慢的突触前多巴胺转运蛋白的封锁发作，并且与立即释放的哌醋甲酯相比，与较低的检测和可爱性风险相关。将十二个健康的成年人随机分配，以接收单剂量立即释放的哌醋甲酯或渗透释放甲酯。选择可产生当量最大浓度（C（Max））值的剂量（40 mg立即释放哌醋甲酯和90 mg渗透释放甲基甲酯）。在两次单独的情况下，在哌醋甲酯给药后获得了10小时，血浆D-甲基苯甲酯水平和对检测/可爱性问卷的反应。多巴胺转运蛋白受体占用物在1、3、5和7小时测量碳11标记的成像剂（Altropane）和正电子发射断层扫描。结果：尽管两种配方的C（最大）值相似，但与直接释放的甲甲化酸酯相比，渗透释放甲基甲酯与最大最大浓度的更长时间，最大CNS多巴胺转运蛋白占用时间更长的时间相关，没有检测/比较。讨论：研究结果表明，口服哌醋甲酯的滥用潜力受到递送速度的强烈影响，而不仅仅是血浆浓度或脑转运蛋白占用量的大小。这些结果提高了对哌醋甲酯在人类中的潜在中心作用的理解，并确定了潜在的滥用甲基甲酯制剂。