Neurotropic activity and safety of methylene-cycloalkylacetate (MCA) derivative 3‑(3-allyl-2-methylenecyclohexyl) propanoic acid

Polyneuropathy involves multiple peripheral nerve injuries, affecting pain, movement, and autonomic functions. Current treatments mainly address neuropathic pain, but lack the ability to reverse nerve injury or promote regeneration. This study investigates a new drug candidate, MCA-13, for its neurotropic and safety properties. The study focuses on MCA-13's ability to induce neurite outgrowth, which is crucial for nerve regeneration and functional recovery. The research assesses the compound's effects on dorsal root ganglia and spinal cord neuronal cultures, along with its safety profile via blood analysis, toxicity evaluations in mice, and off-target pharmacological assessments. The findings suggest MCA-13 has neurotropic potential and a relatively safe profile. Further preclinical studies are warranted to explore its mechanisms and therapeutic efficacy in animal models of polyneuropathy, with the ultimate goal of developing a clinically relevant neurotropic drug.

• 1
  HU-MCA-13 induced neurite outgrowth in PC12 dopaminergic cell cultures, dorsal root ganglion (DRG) sensory neurons and adult rat spinal cord primary cultures.
• 2
  Acute tolerance studies in mice showed no mortality at a high dose of 250 mg/kg, and blood analyses indicated a lack of significant differences in blood count, electrolytes, and coagulation parameters between HU-MCA-13-injected and control mice.
• 3
  In vitro pharmacological profiling revealed that HU-MCA-13 interacts with certain G-protein coupled receptors (GPCRs) such as α2A-adrenergic receptor, Cannabinoid receptors CB1 and CB2, and Histamine H2 receptor, as well as Cyclooxygenase-1 activity.