# Centrally Acting Skeletal Muscle Relaxants Sharing Molecular Targets with Drugs for Neuropathic Pain Management

## TL;DR

This review explores how certain muscle relaxants, like tolperisone, might be repurposed for treating neuropathic pain due to their shared molecular targets with existing pain drugs.

## Contribution

The paper proposes combining VGSC and VGCC blockers, supported by tolperisone's preclinical success in neuropathic pain.

## Key findings

- Tolperisone blocks voltage-gated sodium and calcium channels, relevant to neuropathic pain.
- Combining tolperisone with pregabalin acutely halts neuropathic pain in preclinical studies.
- VGSC and VGCC blockers show potential for improved neuropathic pain treatment when combined.

## Abstract

Treatment of neuropathic pain (NP) remains a challenge in clinical practice because the current treatment approaches produce satisfactory pain alleviation in only 30% of patients. This necessitates developing novel drugs or repurposing existing medications intended to manage other diseases. When the repurposing intendance is chosen, similarity in the pharmacological properties should be hosted by the candidate drugs. Herein, this review sheds light on the mechanisms of certain centrally acting skeletal muscle relaxants (CMRs), specifically tolperisone. So far, data indicate that tolperisone displays voltage-gated sodium channel (VGSC) blocking properties with modulatory effect on voltage-gated calcium channels (VGCCs). These properties have led to recent preclinical research initiatives testing tolperisone in NP, resulting in positive outcomes. Furthermore, the review highlights the currently available VGSC blockers and proposes a strategy based on combining them with VGCC blockers that have been proven for the treatment of NP. This proposal is supported by the fact that tolperisone, in combination with pregabalin, has recently been shown to acutely halt NP.