Article Figures & Data
Figures
- Fig. 1.
Chemical structure of clonidine.
- Fig. 2.
Chemical structures of candidate endogenous imidazoline receptor ligands harmane, IAA-RP, harmalan, and agmatine.
- Fig. 3.
Chemical structures of aminopyrrolines of interest LNP911, LNP906, LNP509, and LNP599.
- Fig. 4.
Chemical structures of I2 receptor ligands 2-BFI, BU224, tracizoline, CR4056, phenyzoline, and idazoxan.
- Fig. 5.
PET imaging of I2 receptors in healthy volunteers treated with the radioligand 11C-BU99008. Data adapted from Tyacke et al. (2018) with permission.
- Fig. 6.
Two mechanisms underlying imidazoline I2 receptor agonist-induced analgesia. I2 receptor agonists can increase the synaptic monoamine (5-HT and norepinephrine) level via MAO inhibition, which can subsequently activate the individual monoaminergic receptors. I2 receptor agonists can also inhibit central glial activity, attenuate the secretion of proinflammatory cytokines, and then attenuate the neural activity of the second-order pain-projecting pathways. 5-HT, serotonin; AR, adrenergic receptor; I2R, I2 receptor.
Tables
Receptor Type Common Ligands Pharmacological Effects Cellular Effect Cellular Action In Vivo Effect In Vivo Action I1 LNP509, LNP599, LNP91, LNP911 Cell viability Is antiproliferative; protects cell viability Blood pressure Reduces blood pressure and heart rate Insulin and adiponectin Stimulates the secretion of adiponectin; increases insulin sensitivity; is insulinotropic Heart arrhythmia Has an antiarrhythmic effect Neurons Increases MAPK activity; decreases GABAA receptor–mediated inhibitory postsynaptic currents Heart failure Improves cardiac performance in congestive heart failure; prevents ventral hypertrophy Glucose and lipid metabolism Reduces insulin resistance, hyperinsulinemia, hypertension, and metabolic syndrome I2 2-BFI, BU224, CR4056, tracizoline, idazoxan, phenyzoline Pain Is antinociceptive in multiple models of chronic pain; enhances the antinociceptive effects of opioids; reduces antinociceptive tolerance and physical dependence of opioids Subjective effects Produces characteristic discriminative stimulus effects specific to I2 receptor activation Neuroprotection Is neuroprotective in a rat cerebral ischemia model Body temperature Reduces body temperature and may involve temperature regulation I3 KU-14R Insulin secretion Facilitates insulin secretion
In this issue
A Review of Imidazoline Receptors
