Amantadine is an antiviral drug that was used to treat influenza in humans. Because of its mode of action, it is also being used for much more including helping dogs and cats with neurologic disease as well as people with Parkinson’s and Alzheimer’s disease. Amantadine is a N-methyl-D-aspartate (NMDA) receptor blocker. In the nervous system, aspartate or glutamate bind to the NMDA receptor in the spinal cord and brain. It’s thought that this action is important in not only maintaining but even exacerbating pain. Amantadine blocks the NMDA receptor which in turn, blocks pain. In dogs and cats, amantadine is being used to treat pain from osteoarthritis, cancer especially osteosarcoma, nerve-based pain as well as chronic pain from declaws. It is also added to pain management protocols when traditional medications do not provide adequate relief.
The newest area of interest is using amantadine is to protect nerve function. The rationale for this is based on blocking the mechanism in the central nervous system (spinal cord and brain) that causes allodynia which is a term used to describe pain caused by a normally non-noxious stimulus. Researchers Kim and Jeong found that activation of the NMDA receptor is associated with altered microglia activity and prolongation of allodynia caused by a mechanical injury to the spinal cord. Another research team lead by J. Chen found that suppressing the activation of NMDA receptors during injury can decrease astrocyte activation and lessen the sensation of neuropathic pain. One of the most exciting uses is to help people with diabetic neuropathy. In 2016, a study published in the Journal of Neurophysiology showed for the first time that “…NMDA receptor-dependent phosphorylation of MAPKs in the spinal cord neurons and microglia contribute to the establishment and long-term maintenance of painful diabetic hyeralgesia…”
Based on this rational, amantadine is being given to dogs with degenerative myelopathy and canine cognitive dysfunction. My own dog has shown tremendous improvement after starting amantadine. Buddy is a 13-year-old shepherd mix that I adopted 12 years ago. In the last year, he started dragging his back legs to the point of wearing the fur off the top of his paws. He also became increasingly confused, got stuck in strange places and did not respond appropriately to commands. Blood work and X-rays were all within normal limits except for some mild osteoarthritis. I treated him with grapiprant, gabapentin, physical therapy and supplements but his condition continued to deteriorate. I stopped the gabapentin because in rare types of neurologic disease, it can make the condition worse. Amantadine usually takes several weeks to take effect but Buddy showed improvement within a few days. He was able to stand on the slippery clinic floors without sinking. He was also more alert. He stopped getting lost and responded more rapidly when called.
Amantadine is excreted through the kidneys. Unfortunately, this drug has many side effects. At low doses, agitation, gas, diarrhea, and other anticholinergic effects including dry mouth can occur. At higher doses, seizures, urine retention and increased heart rate have been observed. It should be used with caution in dogs with renal disease, hepatic disease, congestive heart failure, active psychoses, seizures and glaucoma.
Because of the side effects, I started Buddy on a low dose of amantadine. I soon noticed that the effect only lasted about twelve hours. When I increased his dose to twice a day, he became agitated. The agitation quickly resolved when I decreased the dose. After I few days, I increased it again by half as much and he is doing well.
-Chen, J.J., et al, Effects of pre-emptive drug treatment on astrocyte activation in the cuneate nucleus following rat median nerve injury. Pain. 2010 Jan;148(1):158-66.
-Daulhac L 1, et al, Diabetes-induced mechanical hyperalgesia involves spinal mitogen-activated protein kinase activation in neurons and microglia via N-methyl-D-aspartate-dependent mechanisms. J Neurophysiol. 2016 Aug 1;116(2)448-55.
-Kim, M.A., et al, Chronological changes of mechanical allodynia and spinal microglia activation by an intrathecal injection of MK-801. Neuroreport. 2013 Aug 7;24(11):585-9
-Plumb’s Veterinary Drugs @2019 Educational Concepts, L.L.C. dba Brief Media