Fig. 4: Monomer and oligomer conformations of the 5-HT_2AR.

The 5-HT_2AR is expressed as single monomers but also as receptor complexes constituted by two or more receptor units. The binding of a drug to one of the monomers of the complex could induce positive, negative or no cooperativity for the binding to other monomers with the complex. For example, the binding of the antagonist MDL100907 or the inverse agonist altanserin to one of the binding pockets of the homodimer introduces negative allosteric effects on the binding of the same drug to the second binding pocket⁴³. This negative cooperativity would prevent the identification of the total number of binding sites. In contrast, the binding of hallucinogenic 5-HT_2AR agonist such as (±)DOB and LSD to receptor homodimers does not modify the estimation of the total number of binding sites⁴³. Higher order 5-HT_2AR oligomeric and heteromeric complexes of 5-HT_2ARs with other GPCRs are also feasible^24,42.