Guanfacine, an anti-hypertensive agent, is a selective agonist of α2A-adrenoceptor (α2AR) with a Kd value of 31 nM, displaying 60-fold selectivity over α2B-adrenoceptors.
In 5-choice serial reaction-time task (5-CSRTT), guanfacine treated at a low dose has been shown to increase attention in NK1R knockout mice, but not in WT mice. Guanfacine treated at a high dose reduced impulsivity in both NK1R-/- and WT mice [1].
Guanfacine has been demonstrated to reduce alcohol intake in high alcohol-consuming rats. Guanfacine treatment has been revealed to decrease the alcohol deprivation effect (ADE) and reduce the alcohol seeking and cue/priming-mediated reinstatement of alcohol seeking in rats [2].
Guanfacine has shown to reduce C-fiber-evoked field potentials in a rat model induced by spinal nerve ligation, the effect of which was reduced by treatment of receptors of the delta (DOR) antagonist naltrindole, but not by treatment of receptors of the mu (MOR) antagonist CTOP. On the contrary, DOR agonist deltorphin II, but not MOR agonist DAMGO-mediated depression of C-fiber-evoked spinal field potentials was increased by guanfacine. Additionally, co-administration of guanfacine at a low dose with deltorphin II could enhance the effect of deltorphin II mediated production of stable thermal and mechanical antinociception in nerve-ligated rats [3].
References:
1.Pillidge K1, Porter AJ, Dudley JA, Tsai YC, Heal DJ, Stanford SC. The behavioural response of mice lacking NK1 receptors to guanfacine resembles its clinical profile in treatment of ADHD. Br J Pharmacol. 2014 Oct;171(20):4785-96. doi: 10.1111/bph.12860.
2.Fredriksson I1, Jayaram-Lindström N1, Wirf M1, Nylander E1, Nyström E1, Jardemark K2, Steensland P1.Evaluation of Guanfacine as a Potential Medication for Alcohol Use Disorder in Long-Term Drinking Rats: Behavioral and Electrophysiological Findings. Neuropsychopharmacology. 2014 Oct 31. doi: 10.1038/npp.2014.294. [Epub ahead of print]
3.Aira Z1, Barrenetxea T1, Buesa I1, Azkue JJ2. Plasticity of α2-adrenergic spinal antinociception following nerve injury: Selective, bidirectional interaction with the delta opioid receptor. Brain Res. 2015 Jan 12;1594:190-203. doi: 10.1016/j.brainres.2014.11.009.