Dilemma of Addiction and Respiratory Depression in the Treatment of Pain: A Prototypical Endomorphin as a New Approach.

Dilemma of Addiction and Respiratory Depression in the Treatment of Pain: A Prototypical Endomorphin as a New Approach.

Publication date: Jun 05, 2019

Although mu-opioid receptor agonists have been the mainstay of analgesic regimens for moderate to severe pain, they are associated with serious side effects, risks, and limitations. We evaluate the most serious risks associated with conventional opioids and compare these with the pharmacology of CYT-1010, a prototypical endomorphin and mu-opioid receptor agonist.

Addiction and respiratory depression are serious risks of traditional mu-opioid analgesics. Mitigation strategies have been inadequate at addressing the opioid crisis and may interfere with the effective treatment of pain. Improved understanding of mu-opioid receptor biology and the discovery in 1997 of an additional and unique family of endogenous opioid peptides (endomorphins) have provided a pathway for dissociating analgesia from opioid-related adverse events and developing new classes of mu-opioid receptor agonists that use biased signaling and/or target novel sites to produce analgesia with reduced side effect liability. Endomorphin-1 and -2 are endogenous opioid peptides highly selective for mu-opioid receptors that exhibit potent analgesia with reduced side effects. CYT-1010 is a cyclized, D-lysine-containing analog of endomorphin-1 with a novel mechanism of action targeting traditional mu- and exon 11/truncated mu-opioid receptor 6TM variants. CYT-1010 preclinical data have demonstrated reduced abuse potential and analgesic potency exceeding that of morphine. In an initial phase 1 clinical study, CYT-1010 demonstrated significant analgesia vs baseline and no respiratory depression at the dose levels tested.

CYT-1010 and other novel mu-opioid receptor agonists in clinical development are promising alternatives to conventional opioids that may offer the possibility of safer treatment of moderate to severe pain.

Webster, L. and Schmidt, W.K. Dilemma of Addiction and Respiratory Depression in the Treatment of Pain: A Prototypical Endomorphin as a New Approach. 03624. 2019 Pain Med.

Concepts Keywords
Abuse Potential Depression Treatment
Analgesia Pain
Analgesic Opioids
Analgesics Branches of biology
Analog Phenols
Endogenous Opioid Opioid receptors
Exon RTT
Inadequate Morphinans
Lysine Ethers
Morphine Endomorphin
Mu Opioid Receptor Μ-opioid receptor
Opioid Morphine
Opioid Receptor Agonist Tonazocine
Opioids
Pain
Peptides
Pharmacology
Receptors
Respiratory Depression

Semantics

Type Source Name
disease MESH development
drug DRUGBANK Morphine
drug DRUGBANK D-Lysine
disease DOID analgesia
disease MESH Respiratory Depression

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