Receptor signaling allosteric effect

Thus, the non-zero , term reduces the effect of a on the pA2 estimate. It can be seen that when receptor signaling is blocked by the allosteric modulator ( = 0), Equation 7.34 reduces to Equation 7.32. 

As discussed in Chapter 7, antagonists may bind to a separate loci on the receptor and thereby allosterically modify the affinity of the receptor for the agonist. The maximal change in the agonist affinity is denoted by a term a. It is useful to distinguish allosteric effects in terms of whether the modulator affects signaling and affinity or just affinity. In the latter situation, the modulator produces parallel shifts to the right of the concentration response curve up to a maximal point. This is discussed in Section 7.4.1 (t, = 1). Under these circumstances, the curve for... 

Current treatment for insomnia centers on GABAa ( aminobutyric acid) receptor signalling and includes GABAa receptor positive allosteric modulators (PAMs), for example, agents such as zolpidem (Ambien, 2). While zolpidem has been off patent since 2007, another similar compound, eszopiclone (Lunesta, 3), is still prescribed for insomnia, with sales in 2010 reaching almost 1 biUion. These compounds are classified as sedative-hypnotics and their side effecTs include cognitive impairment, musculoskeletal impairment, and mild dysphoria. ... 

---