Additional in vitro studies found similar conclusions, where adult sensory neurons transfected with plasmid overexpression of M1R showed inhibited neurite outgrowth, which appeared to show a partial reversal with subsequent introduction of pirenzepine.
However, while the evidence certainly points to pirenzepine being a neuroprotective agent, there does not seem to be any evidence the drug alters the endogenous muscarinic signaling pathway. “Our work so far has shown no role for altered muscarinic receptor signaling in the etiology of diabetic neuropathy,” Dr. Fernyhough told Practical Pain Management.
There are also other nonneuronal cells in the body that express M1R, which suggests there may be additional or alternative pathways by which M1R antagonism triggers these neuroprotective benefits. Keratinocytes are of particular interest in this area given their rich cholinergic phenotype, expressing M1R, choline acetyltransferase (ChAT), and AChE.3