Moxonidine, a Mixed a₂‐Adrenergic and Imidazoline Receptor Agonist, Identifies a Novel Adrenergic Target for Spinal Analgesia

Abstract

Moxonidine is a mixed alpha(2)-adrenergic and imidazoline receptor agonist with an improved side effect profile compared to clonidine. Intrathecal (i.t.) moxonidine has been found to possess analgesic activity that, in contrast to the majority of alpha(2)-adrenoceptor (alpha(2)AR) agonists, does not require activation of the alpha(2A)AR subtype, which mediates many of the side effects associated with alpha(2)AR use. In addition, moxonidine (i.t.) interacts in a synergistic manner with opioid agonists and this synergy is retained in neuropathic pain states. Moxonidine may therefore be clinically useful in the treatment of chronic neuropathic pain, either alone or as a coadjuvant with opioids.

Agonists and Antagonists Targeting the Different α2-Adrenoceptor Subtypes

“…Modifications firstly concerned the aromatic core by introducing various substituents or by replacing the phenyl ring with the pyridine (60), pirimidine (for example moxonidine (61) [143]) or thiophene ones (62), or else by enlarging it (63) as in the case of tizanidine (18), recommended as premedication for patients undergoing epidural catheterization [144].…”

Polyanalgesic Consensus Conference 2007: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

“…Moxonidine, a mixed alpha‐2‐adrenergic and imidazoline receptor agonist, may be clinically advantageous for chronic neuropathic pain when administered alone or in conjunction with opioid therapy (79). The analgesic effects of IT moxonidine are not dependent on activation of the alpha‐2A adrenoceptor subtype (79). Intrathecal moxonidine thus has a better side‐effect profile than clonidine.…”

“…Intrathecal moxonidine thus has a better side‐effect profile than clonidine. Moxonidine‐administered IT displays a synergistic activity with opioid agonists that persists during neuropathic pain (79). Moxonidine has been withdrawn from the market after a controlled study suggested that oral administration in heart failure patients resulted in increased morbidity and mortality (80).…”

Moxonidine for tramadol withdrawal symptoms during detoxification

“…However, multiple studies have revealed the potential role of α2 receptor agonists, including moxonidine, in the management of pain:8 when introduced intrathecally, it was found to have an analgesic effect without acting on the α2a receptor subtype, which mediates most of the side effects associated with clonidine 9. Similarly, imidazoline receptors have been detected in brain areas responsible for perception of pain and have also been found to interact with the opioid system in the central nervous system 10.…”