Description
Why SB-243213 over other 5-HT2C antagonist RC candidates
- In summary, the most potent 5-HT2C antagonists in order is: SB-243213 ∼ SB-228357 > SB-242084 > FR-260010
- Others in the SB series and other 5-HT2C antagonists like RS-102221 are simply less potent to be considered. These four are the only ones that are brain-penetrant, selective, have very high affinity, and good oral availability [x]
- The three SB series compounds named above are all pKi = 9.0, which is equivalent to Ki = 1.0 nM [x]
- FR-260010 also has a very high affinity (Ki = 1.1 nM), but unfortunately has a short half-life. FR-260010 is >90% eliminated by hour 2 [x]
- Both SB-243213 and SB-228357 are active at lower oral doses (ID50 = 0.7 mg/kg po) than SB-242084 (2.0 mg/kg po) despite having the same affinity, indicating better pharmacokinetics [x]
- SB-243213 and SB-228357 are quite similar in affinity, pharmacokinetics, and duration, but SB-243213 is a significantly more cost effective synthesis, making it the best overall option out of the 5-HT2C antagonists
- SB-243213 is an inverse agonist at the 5-HT2C Gβγ-protein pathway and an antagonist for the Gq-protein pathway [x]
- SB-243213 is 160x selective for 5-HT2C over 5-HT2A and 100x selective for 5-HT2C over 5-HT2B [x]
- SB-243213 has a duration of action of >8 h [x]
Clorgyline