Vocacapsaicin hydrochloride Usage And Synthesis

Clinical research

A triple-blind, randomized, placebo-controlled Phase II trial (NCT03599089) was conducted to assess the safety and efficacy of vocacapsaicin for postoperative pain management. A total of 147 patients undergoing bunionectomy were randomly assigned into four groups to receive different concentrations of vocacapsaicin and placebo. The experimental groups were given vocacapsaicin at concentrations of 0.30mg/ml, 0.15mg/ml, and 0.05mg/ml; the control group was given a placebo. The results showed that the 0.30mg/ml vocacapsaicin group had significant effects in reducing resting pain, reducing opioid demand, reducing opioid consumption, and reducing pain within one week after surgery. Within two weeks postoperatively, the average numerical rating scale pain scores for both the placebo group and the 0.30mg/ml vocacapsaicin group in resting and walking conditions demonstrated that the vocacapsaicin group had an initial increase in pain postoperatively, but then showed a sustained analgesic effect. Patients treated with vocacapsaicin (0.30mg/ml) discontinued opioid use earlier than those in the placebo group, with patients treated with vocacapsaicin no longer requiring opioids after five days. In summary, a single topical administration of vocacapsaicin during surgery can significantly reduce pain and opioid consumption for at least 96 hours postoperatively, with good tolerability and safety.

Description

Vocacapsaicin, formerly designated as CA-008 HCl, is a novel prodrug of trans-capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) being developed as a nonopioid, site-specific treatment for postsurgical pain management. It is designed to provide long-lasting (at least 96?h) postsurgical analgesia following a single intraoperative administration. The free base form of vocacapsaicin rapidly cyclizes under physiological conditions to yield active capsaicin and CA-101 (cyclic urea) as the sole conversion products. Vocacapsaicin was developed to improve the solubility profile of capsaicin and allow for an aqueous formulation that could be simply administered at the wound site to achieve a long-lasting analgesic effect. Vocacapsaicin has little or no pharmacologic activity as the intact prodrug and is rapidly converted to capsaicin[1].

Biological Activity

Vocacapsaicin (CA-008) hydrochloride, a proagent of Capsaicin, is a first-in-class non-opioid TRPV1 agonist. Vocacapsaicin hydrochloride can provide meaningful and long-lasting pain relief.

Mechanism of action

Vocacapsaicin is an innovative water-soluble prodrug that rapidly releases capsaicin. The design of this prodrug aims to activate TRPV1 receptors through topical administration. Capsaicin can induce a long-term non-responsive state in C-fibers, providing a sustained analgesic effect without affecting sensation, proprioception, or muscle strength.

References

[1] Tarra Knotts. “Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models.” Journal of Orthopaedic Research 40 10 (2022): 2281–2293.