Mendelson John E, McGlothlin Dana, Harris Debra S, Foster Elyse, Everhart Tom, Jacob Peyton, Jones Reese T
Addiction Pharmacology Research Laboratory, The California Pacific Medical Center Research Institute, St. Luke's Hospital, 7th floor, 3555 Cesar Chavez Street, San Francisco, CA 94110, USA.
BMC Clin Pharmacol. 2008 Jul 21;8:4. doi: 10.1186/1472-6904-8-4.
We studied the pharmacology of l-methamphetamine, the less abused isomer, when used as a nasal decongestant.
12 subjects self-administered l-methamphetamine from a nonprescription inhaler at the recommended dose (16 inhalations over 6 hours) then at 2 and 4 (32 and 64 inhalations) times this dose. In a separate session intravenous phenylephrine (200 microg) and l-methamphetamine (5 mg) were given to define alpha agonist pharmacology and bioavailability. Physiological, cardiovascular, pharmacokinetic, and subjective effects were measured.
Plasma l-methamphetamine levels were often below the level of quantification so bioavailability was estimated by comparing urinary excretion of the intravenous and inhaled doses, yielding delivered dose estimates of 74.0 +/- 56.1, 124.7 +/- 106.6, and 268.1 +/- 220.5 microg for ascending exposures (mean 4.2 +/- 3.3 microg/inhalation). Physiological changes were minimal and not dose-dependent. Small decreases in stroke volume and cardiac output suggesting mild cardiodepression were seen.
Inhaled l-methamphetamine delivered from a non-prescription product produced minimal effects but may be a cardiodepressant.
我们研究了较少被滥用的异构体左旋甲基苯丙胺用作鼻减充血剂时的药理学特性。
12名受试者通过非处方吸入器自行使用左旋甲基苯丙胺,先按照推荐剂量(6小时内吸入16次),然后分别以该剂量的2倍(32次吸入)和4倍(64次吸入)使用。在另一次实验中,静脉注射去氧肾上腺素(200微克)和左旋甲基苯丙胺(5毫克),以确定α激动剂的药理学特性和生物利用度。测量了生理、心血管、药代动力学和主观效应。
血浆左旋甲基苯丙胺水平常常低于定量水平,因此通过比较静脉注射和吸入剂量后的尿排泄量来估计生物利用度,对于递增暴露量(平均4.2±3.3微克/次吸入),估计的给药剂量分别为74.0±56.1、124.7±106.6和268.1±220.5微克。生理变化极小且不依赖剂量。观察到每搏输出量和心输出量略有下降,提示有轻度心脏抑制作用。
从非处方产品吸入的左旋甲基苯丙胺产生的效应极小,但可能是一种心脏抑制剂。