ABT 724 trihydrochloride is a highly selective D4 dopamine agonist [1][2], with an EC50 of 281 nM in increasing the binding activity of GTPγS in CHO cells transfected with human D4 receptors, and of 12.4 nM in increasing Ca2+ influx of HEK-293 cells co-transfected with a G protein (Gαq05) and rat/human D4 receptors [3].

The neurotransmitter dopamine (DA) is important for regulating functions of human T cell. Through D1/D5, D2, and D3 receptors, DA can activate resting T cells by stimulating the expression of surface integrins and the release of cytokines. By down-regulating nonreceptor tyrosine kinases, DA can inhibit the proliferation of activated T cells. Stimulation of dopamine D4 receptors can induce T cell quiescence [1].

With the presence of the D4 receptors, T cells were treated with the specific D4 DA agonist PD 168,077 at a concentration of 1 ?M at the onset of 48 h of TCR stimulation with anti-CD3/CD28 so that the D4 DA agonist remained throughout this period, The proliferation of these cells was significantly inhibited. This result was from the evidence of [3H]thymidine incorporation. When treated with another D4 DA agonist, ABT 724 trihydrochloride at a concentration of 1 ?M, T cells also showed similar results [1].

Clozapine has high affinity for the dopamine D4 receptor [4]. Compared to treatment with clozapine alone, clozapine plus 50 ?M or 25 ?M ABT-724 significantly increase the locomotor activity of zebrafish larvae. The effect of ABT-724 to protect larvae from the clozapine-induced hypoactivity is in a dose-dependent fashion [5].

References:
[1].  Sarkar C, Das S, Chakroborty D, et al. Cutting Edge: Stimulation of dopamine D4 receptors induce T cell quiescence by up-regulating Kruppel-like factor-2 expression through inhibition of ERK1/ERK2 phosphorylation. J Immunol, 2006, 177(11):7525-9.
[2].  Melis MR, Succu S, Mascia MS, et al. PD-168077, a selective dopamine D4 receptor agonist, induces penile erection when injected into the paraventricular nucleus of male rats. Neurosci Lett, 2005, 379(1):59-62.
[3].  Sanna F, Contini A, Melis MR, et al. Role of dopamine D4 receptors in copulatory behavior: Studies with selective D4 agonists and antagonists in male rats. Pharmacol Biochem Behav, 2015, 137:110-8.
[4].  Arranz M, Collier D, Sodhi M, et al. Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet, 1995, 346(8970):281-2.
[5].  Boehmler W, Carr T, Thisse C, et al. D4 Dopamine receptor genes of zebrafish and effects of the antipsychotic clozapine on larval swimming behaviour. Genes Brain Behav, 2007, 6(2):155-66.