Potential for antipsychotic and psychotomimetic effects of A<inf>2A</inf>receptor modulation

The discovery of antagonistic interactions between A2Aadenosine receptors and D2dopamine receptors in the ventral striatum suggested that A2Areceptor activation might modulate the antipsychotic effects of dopamine receptor antagonists and could provide an opportunity for the development of A2Areceptor agonists as novel antipsychotic drugs. However, there is limited evidence from preclinical and clinical studies that A2Areceptor agonists can exert antipsychotic effects. Furthermore, it remains unclear whether A2Areceptor agonists possess a sufficient safety margin or whether their potent hypotensive effects or extrapyramidal side effects would limit their therapeutic utility as antipsychotic agents. The interaction between A2Areceptors and D2receptors also raises the possibility that A2Areceptor antagonists, which hold considerable promise as antiparkinsonian agents, may have dose-limiting psychotomimetic side effects. Preclinical studies using selective A2Areceptor antagonists suggest that this class of compound has a low propensity to elicit psychotomimetic side effects or exacerbate those induced by D2receptor agonists.