Effect of antidepressant and narcoleptic drugs on N-isopropyl p-iodoamphetamine biodistribution in animals.
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.
D000662:Amphetamines / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D007099:Imipramine / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000378:metabolism; D020367:Iofetamine; D008297:Male; D010624:Phenelzine / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology*; D014018:Tissue Distribution
D000662:Amphetamines; D007457:Iodine Radioisotopes; D010627:Phenethylamines; D011943:Receptors, Adrenergic, beta; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D012642:Selegiline; D020367:Iofetamine; D010624:Phenelzine; D007099:Imipramine