TAAR2 Inhibitors

Chemical inhibitors of TAAR2 can act through various mechanisms to impede the receptor's function. Epinephrine, for example, competes for binding sites on TAAR2, effectively preventing the receptor from interacting with its natural ligands. This competitive binding results in a functional inhibition of TAAR2's signaling activity. Similarly, both amphetamine and methamphetamine lead to a release of endogenous amines, which can saturate TAAR2 and preclude its activation. Pseudoephedrine indirectly agonizes the receptor, which over time can cause TAAR2 to become less responsive to its endogenous triggers, while chlorpheniramine directly blocks the receptor sites, curtailing TAAR2's ability to be activated by its natural agonists.

Further, cyproheptadine acts as an inverse agonist to stabilize TAAR2 in an inactive state, which hinders the receptor's natural activation cycle. Phentermine triggers a depletion of endogenous amines through their expedited release and metabolism, which diminishes their availability to activate TAAR2, thereby inhibiting the receptor. Clenbuterol binds with high affinity to TAAR2, preventing the natural ligands from activating the receptor. Methylphenidate and atomoxetine inhibit TAAR2 by blocking the reuptake of monoamines like dopamine and norepinephrine, respectively, which leads to higher synaptic concentrations of these amines. This increase can result in the occupation of TAAR2 receptor sites, impeding the receptor's activation by its natural ligands. Similarly, selegiline inhibits TAAR2 by irreversibly inhibiting monoamine oxidase B, increasing levels of dopamine and other monoamines that can occupy and inhibit TAAR2.