# Respiratory and Cardiovascular Activity of LENART01, an Analgesic Dermorphin–Ranatensin Hybrid Peptide, in Anesthetized Rats

## TL;DR

LENART01, a hybrid peptide, shows pain-relieving properties with fewer dangerous side effects like apnea compared to traditional opioids in rats.

## Contribution

LENART01 is a novel hybrid peptide with analgesic activity and reduced respiratory depression compared to dermorphin.

## Key findings

- LENART01 caused apnea in 70% of anesthetized rats but with less intensity than dermorphin.
- The hybrid peptide induced less frequent sighing and lower dependence on vagus nerve mu opioid receptor activation.
- LENART01 significantly increased blood pressure in tested animals.

## Abstract

Opioids are among the most effective drugs for treating moderate to severe pain. Unfortunately, opioid use, even short-term, can lead to addiction, tolerance, overdose, and respiratory depression. Therefore, efforts to design and develop novel compounds that would retain analgesic activity while reducing side effects continue unabated. The present study was designed to investigate the respiratory and cardiovascular effects of the hybrid peptide LENART01, which has evidenced potent antinociceptive and antimicrobial activity. This hybrid peptide, composed of N-terminally located dermorphin and C-terminal modified ranatensin pharmacophore, was tested in vivo in anesthetized rats. The main effect of LENART01 was apnea in 70% of examined animals, sighing, and a significant increase in blood pressure. Interestingly, the hybrid induced sighs less frequently than ranatensin, and apnea dependent on vagus nerve mu opioid receptor activation much less frequently and less intensely than dermorphin itself. This shows that LENART01 is a safer opioid system-related agent as compared to dermorphin for its prospective use in the treatment of pain.