Background:
stronger analgesic effect than
morphine without causing side effects brought about by morphine-like drugs. Functional opiorphin analogs have been created to enhance its metabolic stability and preserve its potent analgesic
effect.
Objective:
We conducted a systematic review to summarize all opiorphin analogs and identify
those with the strongest metabolic stability and antinociceptive effect.
Methods:
From a total of 122 articles, 11 made it to the quantitative synthesis phase. The included articles were categorized into the type of modifications used to improve the metabolic stability of the peptide, metabolism and toxicity profile, drug absorption and in vitro cytotoxicity, antinociceptive effect, the opiorphin analogs’ administration in animals or humans, and the type of
the test used to test the antinociceptive effect.
Results:
The substitution of natural amino acid with a non-natural amino acid, side-chain modifications, or D-aminoacid substitution were the most used type of peptide modification to create
opiorphin analogs. STR-324 and PEGylated liposomes loaded with opiorphin showed the best
metabolism and toxicity performance. [C]-[(CH2)6]-QRF-[S-O-(CH2)8]-R showed high stability in
human plasma and stronger inhibitory potency. YQRFSR and PEGylated liposomes loaded with
opiorphin showed a stronger antinociceptive effect than the parent opiorphin or morphine, with an
analgesic effect of PEGylated liposomes lasting more than 50%. Intravenous administration was
the preferred method of opiorphin analog administration, and different tests were used to test the
antinociceptive effect.
Conclusion:
This paper presents the first systematic review discussing opiorphin and opiorphin
analogs and identifies the most promising candidates for future research.