Presented at the 2012 AAPM Annual Meeting « Back

Agmatine—A Century-Old Newcomer for Neuropathic Pain

Gad M. Gilad, PhD, gmgilad@gmail.com¹, Varda H. Gilad, Neuroscientist¹, (1) Gilad&Gilad LLC, Reseda, California

Primary nerve damage, the underlying cause of neuropathies, sets in motion destructive molecular reactions that can spread to parent nerve cells and beyond and lead to degeneration. Not surprisingly, several molecular mechanisms implicated in nerve degeneration are also suspects in neuropathic pain. This suggested that treatments aimed at neuroprotection would prove a novel strategy for neuropathic pain reduction. It was further postulated that a single neuroprotective agent capable of interacting simultaneously with multiple molecular targets would be a preferred therapeutic for neuropathies. According to this concept, it was proposed that agmatine might constitute such a candidate [1,2]. Agmatine, decarboxylated arginine [(NH2(CH2)4NH2C(NH=)NH], can interact with multiple molecular targets critical for both neuroprotection and neuropathic pain reduction. These include: (A) modulating several neurotransmitter receptors; (B) blockade of key ion transport channels; (C) regulating nitric oxide (NO) production; (D) inhibiting protein ADP-ribosylation; (E) modulating polyamine metabolism; (F) inhibiting matrix metalloproteases (MMPs); (G) blocking advanced glycation end products (AGEs) formation [2,3]. A recent clinical study, published in Pain Medicine [2], suggests that compared to current therapeutics, agmatine provides a superior solution for a safe (lacking adverse effects) and effective treatment in lumbar disc-associated radiculopathy. These findings are considered a proof-of-concept landmark for using agmatine in other neuropathies. Accordingly, two clinical trials now in progress are designed (conforming to the principles of the World Medical Association Helsinki Declaration) to assess the effectiveness of agmatine in chemotherapy-induced neuropathy and in small fiber neuropathy. Interim findings of these trials will be included in this overview poster presentation. References: 1)Fairbanks CA, Schreiber KL, Brewer KL, et al. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury. Proc Natl Acad Sci USA 2000;97:10584-10589. 2)Keynan O, Mirovsky Y, Dekel S, et al. Safety and efficacy of dietary agmatine sulfate in lumbar disc-associated radiculopathy. An open label, dose-escalating study followed by a randomized, double-blind, placebo-controlled trial. Pain Med 2010;11:356–36 3)Halaris A, Plietz J. Agmatine: metabolic pathway and spectrum of activity in brain. CNS Drugs 2007;21:885-900.

Funding: Funding received from Gilad&Gilad LLC, Reseda, California