| Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressive disorder, tic disorders and irritability associated with autism. See also [1].
G-protein coupled receptor for 5-hydroxytryptamine (serotonin) [1][2][3]. Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD)[4]. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors[4]. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways[4]. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores[3], [4]. Affects neural activity, perception, cognition and mood [5]. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances.
Crystal structure of 5-HT2AR in complex with aripiprazole (7voe).
Aripiprazole binding site.
- ↑ Stam NJ, Van Huizen F, Van Alebeek C, Brands J, Dijkema R, Tonnaer JA, Olijve W. Genomic organization, coding sequence and functional expression of human 5-HT2 and 5-HT1A receptor genes. Eur J Pharmacol. 1992 Oct 1;227(2):153-62. PMID:1330647
- ↑ Knauer CS, Campbell JE, Chio CL, Fitzgerald LW. Pharmacological characterization of mitogen-activated protein kinase activation by recombinant human 5-HT2C, 5-HT2A, and 5-HT2B receptors. Naunyn Schmiedebergs Arch Pharmacol. 2009 May;379(5):461-71. doi:, 10.1007/s00210-008-0378-4. Epub 2008 Dec 5. PMID:19057895 doi:https://dx.doi.org/10.1007/s00210-008-0378-4
- ↑ 3.0 3.1 Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I. Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur J Pharmacol. 2008 Oct 10;594(1-3):32-8. doi: 10.1016/j.ejphar.2008.07.040., Epub 2008 Jul 30. PMID:18703043 doi:https://dx.doi.org/10.1016/j.ejphar.2008.07.040
- ↑ 4.0 4.1 4.2 4.3 Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, Lansu K, Schools ZL, Che T, Nichols DE, Shoichet BK, Dror RO, Roth BL. Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell. 2017 Jan 26;168(3):377-389.e12. doi: 10.1016/j.cell.2016.12.033. PMID:28129538 doi:https://dx.doi.org/10.1016/j.cell.2016.12.033
- ↑ Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature. 2008 Mar 6;452(7183):93-7. doi: 10.1038/nature06612. Epub 2008 Feb 24. PMID:18297054 doi:https://dx.doi.org/10.1038/nature06612
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