PT  - JOURNAL ARTICLE
AU  - G. Patrick Hussmann
AU  - Kenneth J. Kellar
TI  - A New Radioligand Binding Assay to Measure the Concentration of Drugs in Rodent Brain Ex Vivo
AID  - 10.1124/jpet.112.198069
DP  - 2012 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.112.198069
4099  - http://jpet.aspetjournals.org/content/early/2012/08/16/jpet.112.198069.short
4100  - http://jpet.aspetjournals.org/content/early/2012/08/16/jpet.112.198069.full
AB  - We have developed a new radioligand binding assay method to measure the concentration of non-radiolabeled drugs in the brain ex vivo. This new method fuses the concepts of standard competition and saturation binding assays, and utilizes a transformed version of the Cheng-Prusoff equation to calculate the drug concentration. After testing the validity of this method, we demonstrated its utility by measuring the brain concentration of sazetidine-A, a newly developed nicotinic receptor ligand, and its elimination rate after a single subcutaneous administration. Our results indicate that sazetidine-A reaches brain concentrations that are known to occupy and desensitize the majority of nAChR binding sites. Furthermore, using this method, we estimated the half-life of sazetidine-A in the rat brain to be ~65 min. It is important to note that the method described here to measure sazetidine-A in brain should be generalizable to other drugs acting at any receptor that can be reliably measured with a radiolabeled ligand.