Moretti J L, Holman B L, Delmon L, Carmel A, Johnson D, Moingeon P, Blau M
J Nucl Med. 1987 Mar;28(3):354-9.
N-isopropyl p-iodoamphetamine (IMP) demonstrates a high affinity for lung and brain during the first pass following intravenous injection. Its high brain affinity has been used to advantage for cerebral perfusion imaging, but the effects of drugs on IMP distribution could affect its utility. In this study, we determined the effects of the tricyclic antidepressant imipramine and the MAO inhibitors deprenyl and phenelzine on the biodistribution of IMP. We first determined the effect of loading dose and anesthesia on the biodistribution of IMP. In rats, biodistribution was not dependent on loading dose between 0.1 and 1.1 mg/kg. Anesthesia with thiopental and chloral hydrate depressed lung and brain IMP uptake. In rats, preloading doses of imipramine depressed lung uptake but did not result in increased brain IMP uptake; postloading doses of imipramine did not release IMP from the lung. In rabbits, simultaneous or postloading doses of imipramine resulted in release of IMP from the lung with an increase in brain activity. Both mixed A and B MAO inhibitors (phenelzine) and B selective MAO inhibitors (deprenyl) did not affect IMP distribution in rats. Based on the action of imipramine on IMP uptake and clearance in the lung, we postulate that IMP uptake and metabolism within the lung is related to the mixed function oxidase (MFO) system. As the lung is rich in the MFO system in humans, we would also predict from this study that IMP distribution in patients under antidepressant therapy would not be affected by either tricyclic or MAO inhibitor agents apart from the effect of these drugs on cerebral perfusion.
N-异丙基对碘安非他明（IMP）在静脉注射后的首次通过过程中对肺和脑表现出高亲和力。其对脑的高亲和力已被用于脑灌注成像的优势，但药物对IMP分布的影响可能会影响其效用。在本研究中，我们确定了三环类抗抑郁药丙咪嗪以及单胺氧化酶抑制剂司来吉兰和苯乙肼对IMP生物分布的影响。我们首先确定了负荷剂量和麻醉对IMP生物分布的影响。在大鼠中，生物分布在0.1至1.1mg/kg的负荷剂量之间不依赖于负荷剂量。硫喷妥钠和水合氯醛麻醉会降低肺和脑对IMP的摄取。在大鼠中，丙咪嗪的预负荷剂量会降低肺摄取，但不会导致脑IMP摄取增加；丙咪嗪的后负荷剂量不会使IMP从肺中释放出来。在兔子中，同时或后负荷剂量的丙咪嗪会导致IMP从肺中释放出来，同时脑活性增加。A和B混合型单胺氧化酶抑制剂（苯乙肼）以及B型选择性单胺氧化酶抑制剂（司来吉兰）均不影响大鼠中IMP的分布。基于丙咪嗪对肺中IMP摄取和清除的作用，我们推测肺内IMP的摄取和代谢与混合功能氧化酶（MFO）系统有关。由于人类肺中富含MFO系统，我们也可以从本研究中预测，接受抗抑郁治疗的患者中IMP的分布除了这些药物对脑灌注的影响外，不会受到三环类或单胺氧化酶抑制剂的影响。
