Alpha-2C adrenergic receptor

Receptor

Alpha-2-adrenergic receptors include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. Studies in mice revealed that both the alpha2A and alpha2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons; the alpha2A subtype inhibited transmitter release at high stimulation frequencies, whereas the alpha2C subtype modulated neurotransmission at lower levels of nerve activity.

Gene

This gene encodes the alpha2C subtype, which contains no introns in either its coding or untranslated sequences.

Ligands

Agonists

• (R)-3-Nitrobiphenyline (also weak antagonist at α2A and α2B)

Antagonists

• BMY 7378 (also α1D antagonist)
• Brexpiprazole
• JP-1302: selective over α2A, α2B, α2C
• N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide
• Pirepemat
• Quetiapine
• Risperidone
• Mirtazapine
• Spiroxatrine
• Yohimbine derivatives 9 and 10: 43 fold selectivity over α2A, α2B and α1 subtypes

References

References

1. "ADRA2C adrenoceptor alpha 2C [Homo sapiens (human)] - Gene - NCBI".
2. "Entrez Gene: ADRA2C adrenergic, alpha-2C-, receptor".
3. (August 2007). "Alpha2-adrenoreceptors profile modulation. 3.1 (R)-(+)-m-nitrobiphenyline, a new efficient and alpha2C-subtype selective agonist". Journal of Medicinal Chemistry.
4. (2005). "The alpha (1D)-adrenoceptor antagonist BMY 7378 is also an alpha (2C)-adrenoceptor antagonist". Autonomic and Autacoid Pharmacology.
5. (2007). "Pharmacological characterization and CNS effects of a novel highly selective alpha2C-adrenoceptor antagonist JP-1302". Br. J. Pharmacol..
6. (2008). "Identification and SAR around N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, a selective alpha2C adrenergic receptor antagonist". Bioorg. Med. Chem. Lett..
7. (September 2008). "N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity". Neuropsychopharmacology.
8. (November 2006). "Tethered yohimbine analogs as selective human alpha2C-adrenergic receptor ligands". J. Pharmacol. Exp. Ther..