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Antipsychotics

How Goldilocks is partial to dopamine receptors

Nature Reviews Drug Discovery volume 1, page 660 (2002)Cite this article

To clarify this, Milinoff and colleagues looked at the interactions of the drug with the recombinant human dopamine D2 receptor, D2L. Their studies, published in the Journal of Pharmacology and Experimental Therapeutics, report that aripiprazole showed characteristics of a partial agonist in binding-affinity and cyclic-AMP-accumulation studies. Also, partial receptor inactivation reduced the maximum effect of aripiprazole on inhibition of cAMP accumulation at concentrations that did not alter the effect of the agonist dopamine, and increasing concentrations of aripiprazole blocked the action of dopamine equal to the agonist effect of aripiprazole alone. Finally, the efficacy of aripiprazole differed to that of dopamine, depending on the density of D2L receptors; and modulating the density of receptors affected the action of aripiprazole — aripiprazole behaved like an agonist in the presence of a receptor reserve for dopamine, but in its absence behaved like an antagonist.

So, the authors conclude that this, and previous studies (showing the partial agonism of 5-hydroxytryptamine (5-HT)1A serotonin receptors and antagonism of 5-HT2A serotonin receptors), support the model that aripiprazole belongs to a class of treatments known as dopamine–serotonin system stabilizers (DSSs). This partial-agonist activity of aripiprazole at D2 receptors, the authors say, could explain the observed unique activity and the sustained efficacy of the drug.

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ORIGINAL RESEARCH PAPER

  1. Burris, K. D. et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J. Pharmacol. Exp. Ther. 302, 381–389 (2002)

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  1. Simon Frantz
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Frantz, S. How Goldilocks is partial to dopamine receptors. Nat Rev Drug Discov 1, 660 (2002). https://doi.org/10.1038/nrd912

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