High-affinity radioligand

An iodinated radioligand that speeilically labels the agonist high affinity state of 5-HT2 serotonin receptors. J Med Chem 31 5-7, 1988. 

Since oocytes are a transient, small-scale expression system, they are not the best suited for radioligand binding studies as (usually) hundreds of oocytes must be injected to harvest sufficient membranes for such measurements. This is both time-consuming and expensive. However, with high affinity and highly specific activity ligands, the expression of binding sites on the membranes of intact oocytes can be readily quantified (see later). 

The agonist radioligands [ HJnicotine and [ HJepibatidine, which are most commonly used to monitor nAChR numbers, freely cross lipid bilayers. Therefore, they do not discriminate between intracellular and surface nAChRs and the majority of the increase in high-affinity binding sites appears to be intracellular (Whiteaker et al. 1998 Vallejo et al. 2005). It is now appreciated that nicotine can accumulate within cells and a new consensus is emerging that supports an intracellular action of nicotine that enhances assembly and/or maturation of nAChRs (Nashmi et al. 2003 Darsow et al. 2005 Kuryatov et al. 2005 Sallette et al. 2004, 2005 Nashmi and Lester 2007 Fig. 4). 

Figure 2.6. Scatchard plot of the binding of a radioligand to a membrane preparation containing two binding sites. In this diagram, represents a high affinity (K ) low capacity site, whereas represents a low affinity (K ) high...

Recently, the 2-[ F]fluoroethylation of a phenolic desalkyl precursor based on the jSi-AR-selective antagonist ICI 89,406 was realized via a two-step synthesis starting with the [ F]fluorination of ethylene glycol di-p-tosylate. The radiosynthesis yielded (S)-A/-[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-A/ -[4-(2-[ F]fluoroethoxy)-phenyl]-urea 10, representing a potent F-labeled high affinity / i-AR-selective radioligand with a / i-AR-selectivity of >40.000 (Fig. 15) [107],... 

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