Anti-Muscarinic Drugs May Reverse Peripheral Neuropathy

For years, the conventional wisdom was to treat patients with diabetic peripheral neuropathy but there was no possibility of a cure. New research findings suggest that nerve degeneration may be treatable and that the drugs used to improve this painful condition are already on the market, albeit for other conditions.

Antimuscarinic drugs are known for their use in motion sickness, overactive bladder issues, and a variety of other conditions. While many drugs in this class are nonselective antagonists of muscarinic receptors, some agents can selectively target the muscarinic acetylcholine (Ach) type 1 receptor (M1R), like trihexyphenidyl, which often has been prescribed to Parkinson’s patients.

There is strong evidence that M1R could be a significant role-player in nerve degeneration in a litany of axonopathic diseases, including diabetic peripheral neuropathy. The study, published in the Journal of Clinical Investigation,1 findings demonstrate that by blocking the M1R receptor, researchers were able to prevent, and even reverse, the effects of peripheral neuropathy in mice, regardless of the underlying disease causing the neuropathy.

“The antimuscarinic drugs activate a regenerative pathway for nerve repair that can be induced under a variety of stressful conditions, ranging from diabetes to chemotherapy and HIV,” Paul Fernyhough, PhD, professor and acting head of the department of pharmacology and therapeutics at the University of Manitoba in Winnipeg, Canada, told Practical Pain Management.

For Dr. Fernyhough and his colleagues, pirenzepine was a selective M1R antagonist of particular interest,2 given its apparent dose-dependent action (3 to 100 nM) of increasing neurite outgrowth in rats. Similar success was found with another M1R antagonist, VU0255035, although structurally dissimilar to pirenzepine.