pcp site 2 pcp site 2 pcp site 2 is a binding site that was identified as a high-affinity target for phencyclidine (pcp), an anesthetic and dissociative hallucinogen that acts primarily as an nmda receptor antagonist. the site is distinct from the pcp binding site on the nmda receptor (otherwise known as pcp site 1) and the common/main sites on the monoamine transporters (sert, dat, net). it is associated with monoamine reuptake inhibition, and it has been suggested that the site may be an allosteric/regulatory site of the monoamine transporters. phencyclidine, a high-affinity ligand of pcp site 2. rti-4793-14 (hbmp), a ligand with high affinity for the pcp site 2 and high selectivity for this site over the pcp site 1, has been developed. similarly to pcp, rti-4793-1 inhibits monoamine reuptake with moderate potency, but unlike pcp, has very low potency as an nmda receptor antagonist. it shows a profile of a serotonin–norepinephrine–dopamine reuptake inhibitor (sndri). although this was inferred to be related to binding to the pcp site 2, subsequent research found that rti-4793-14 also has considerable affinity for the dat; it does not appear to have been characterized at the sert or net, but may bind to them similarly, and these interactions could potentially explain its monoamine reuptake inhibition as an alternative to the pcp site 2. activity profiles selected ligands, pcp sites, monoamine reuptake, and nmdar inhibition compoundrti-4793-14phencyclidine(+)-mk801indatraline pcp site 237.992.4>100002529 pcp site 1 (nmdar)>360001174.58>20000 5-ht uptake10241424>47004.49 da uptake547347>100003.23 cft binding8501547>150004.32 nisoxetine binding6091662865762.27 nmda-induced current76820.02095 all values are ic50 (nm), except nmda-induced current, which is ic50 (μm). ligand-selectivity in human brain compoundpcp site 1(ki, nm)pcp site 2(ki, nm)site 1 /site 2 (+)-mk-8018.9113670.00078 tenocyclidine19.81970.10 phencyclidine43.81540.28 dexoxadrol9212340.075 tiletamine93170500.0055 ketamine831593880.014 vanoxerine3092568414.5 btcp46436210222.1 benztropine78179233833.4 bupropion101239375192.7 fluoxetine106402167763.4 (–)-cocaine267394230550.063 ligand-selectivity in guinea pig brain compoundpcp site 1(ki, nm)pcp site 2(ki, nm)site 1 /site 2 pargyline>10000003643>274 d-amphetamine8050195941.1 clomipramine63437468413.5 (–)-cocaine282362601446.9 (+)-cocaine>10000006383>157 fluoxetine264590929285 mazindol218993919238 vanoxerine102118316732 benztropine156890183857 xylamine>1000000679>1473 desipramine1195421375.6 nomifensine139456260454 bupropion>1000000704>1420 btcp>10000001083>923 ketamine81347020.17 tiletamine79.313940.057 jmiii41c7092980.0075 jmii79b12.7185570.00068 pca126213271.05 ppa646332002.0