Investigational peptide and peptidomimetic μ and δ opioid receptor agonists in the relief of pain

Abstract

Introduction Current methods for treating prolonged and neuropathic pain are inadequate and lead to toxicities that greatly diminish quality of life. Therefore, new approaches to the treatment of pain states are needed to address these problems. Areas covered The review primarily reviews approaches that have been taken in the peer-reviewed literature of multivalent ligands that interact with both μ and δ opioid receptors as agonists, and in some cases, also with pharmacophores for antagonist ligands that interact with other receptors as antagonists to block pain. Expert opinion Although there are a number of drugs currently on the market for the treatment of pain; none of them are 100% successful. In the authors’ opinion, it is clear that new directions and modalities are needed to better address the treatment of prolonged and neuropathic pain; one drug or class clearly is not the answer for all pain therapy. Undoubtedly, there are many different phenotypes of prolonged and neuropathic pain and this should be one avenue to further develop appropriate therapies.

Neuroprotection Against Hypoxic/Ischemic Injury: δ-Opioid Receptors and BDNF-TrkB Pathway

“…Previous studies on the function of DOR were mainly focused on pain modulation and addiction with little conclusive information on its other functions [7-10]. Our recent studies have gained substantial data to show that DOR is a critical neuroprotector in the brain under hypoxic/ischemic conditions.…”

“…Since its cloning in the early 1990s [5, 6], past functional studies were mostly focused on pain modulation and addiction [7-10]. Although scattered studies on other functions of DOR can be found in the literature, the outcomes and conclusions of these studies are inconsistent, and sometimes very contradictory.…”

Effects of Methyl and Halogens in Analgesic Peptide Molecules for Their Potent Agonist Activities at MOR/DOR and Antagonist Activity at NK1R

“…opioid drugs) cannot treat this problem effectively. In addition, constant use of these drugs has deadly side effects including drowsiness and mental clouding, nausea and emesis, and constipation [1]. Development of analgesic tolerance and hyperalgesia in many patients as the results of taking these drugs are also a serious concern.…”

Enkephalin analogues with N-phenyl-N-(piperidin-2-ylmethyl)propionamide derivatives: Synthesis and biological evaluations

“…The subsequent elongation or truncation modifications of these endogenous peptides led to highly promising opioid agonists. 6,19 Many interesting and useful selective peptide ligands for the opioid receptors have been developed and used extensively. The peptide fragments for our bivalent ligands (Tyr-DAla-Gly-Phe and Dmt-DAla-Gly-Phe) are potent well established opioid ligands.…”