title: Pharmacokinetic computer simulations of the relationship between in vivo and in vitro neuroreceptor subtype selectivity of radioligands.
abstract: Pharmacokinetic computer simulations reveal a discrepancy between the in vivo and in vitro neuroreceptor subtype selectivity of radioligands. For radioligands with an in vitro neuroreceptor subtype selectivity between 0.1 and 10.0, the in vivo neuroreceptor subtype selectivity appears to be constrained to be between 0.1 and 10.0, but, in general, is not equal to the in vitro selectivity. For example, if the in vitro selectivity is 1.0 (that is, the radioligand is nonselective in vitro) the in vivo selectivity may be thought of as a random variable having a significant nonzero probability for values as low as 0.1 or as high as 10.0, with a moderate peak at a value of 1.0. For a radioligand whose in vitro subtype selectivity is greater than 10.0, the in vivo selectivity is bounded above by the in vitro subtype selectivity, but may be several orders of magnitude lower than the in vitro subtype selectivity. Thus, in spite of the discrepancy between the in vivo and in vitro neuroreceptor subtype selectivity of radioligands, there are two useful inferences about the in vivo selectivity that might be drawn from knowledge of the in vitro selectivity: (1) If the in vitro selectivity is between 0.1 and 10.0, then, at best, the in vivo selectivity might be as high as 10.0. (2) If the in vitro selectivity is greater than 10.0, then, at best, the in vivo selectivity might be as high as the in vitro selectivity.
authors.affiliation: Department of Radiology, George Washington University Medical Center, Washington, DC, USA. bzeeberg@science.gmu.edu
authors.forename: B R
authors.initials: BR
authors.lastname: Zeeberg
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D008956:Models, Chemical; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000145:classification / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D008024:Ligands; D019275:Radiopharmaceuticals; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic