O-Phenyl-3-iodotyramine
Chemical compound
From Wikipedia, the free encyclopedia
o-Phenyl-3-iodotyramine (o-PIT) is a drug which acts as a selective agonist for the trace amine-associated receptor 1 (TAAR1).[1] It has reasonable selectivity for TAAR1 but relatively low potency, and is rapidly metabolised in vivo, making it less useful for research than newer ligands such as RO5166017.[2][3][4][5] Its EC50 values have been reported to be 35 nM for the mouse TAAR1,[4][6] 2.4 nM at the rat TAAR1,[6] and 9.5 nM at the human TAAR1.[5]
| |
| Clinical data | |
|---|---|
| Other names | o-PIT; o-Phenyl-iodotyramine; o-Phenyliodotyramine |
| Drug class | Trace amine-associated receptor 1 (TAAR1) agonist |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C14H14INO |
| Molar mass | 339.176 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
o-PIT has been found to produce effects in animals including hypothermia, hypolocomotion, antidepressant-like effects, anxiolytic-like effects, anti-obsessional-like effects, and antipsychotic-like effects, and inhibition of prepulse inhibition (PPI).[1][5][7] These actions may be partially to fully dependent on TAAR1 agonism depending on the effect in question.[5]
TAAR1 agonism has been implicated in modulating the effects of monoamine releasing agents (MRAs) like amphetamines.[8] The MRA 3,4-methylenedioxymethamphetamine (MDMA) is a potent agonist of the mouse TAAR1, whereas the MRA para-chloroamphetamine (PCA) is not a significant agonist of the human TAAR1 or presumably of the mouse TAAR1.[5][9] MDMA-induced in-vivo brain serotonin and dopamine release and hyperlocomotion are augmented in TAAR1 knockout mice relative to normal mice, whereas the in-vivo brain serotonin and dopamine release of PCA are not different between normal mice and TAAR1 knockout mice.[5][10] In the same study, o-PIT blunted the dopamine and serotonin release of PCA in mouse synaptosomes in vitro, an effect that was absent in synaptosomes from TAAR1 knockout mice.[5][10] These findings led to conclusions that TAAR1 agonism by MDMA auto-inhibits and constrains its own effects in rodents.[10][5] Although MDMA is a potent TAAR1 agonist in rodents, it is a very weak and non-significant TAAR1 agonist in humans.[9][11][12][13]