Subacute toxicity evaluations of LPM3480392 in rats, a full μ-opioid receptor biased agonist

Article Pharmacology & Pharmacy

Role of efficacy as a determinant of locomotor activation by mu-opioid receptor (MOR) ligands in female and male mice. II. Effects of novel MOR-selective phenylmorphans with high-to-low MOR efficacy

Edna J. Santos et al.

Summary: A novel set of chiral C9-substituted phenylmorphans with improved MOR selectivity and a range of MOR efficacies have been characterized in vitro and in vivo, showing potential for further behavioral studies in mice.

PHARMACOLOGY RESEARCH & PERSPECTIVES (2023)

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Article Clinical Neurology

Body size and brain volumetry in the rat following prolonged morphine administration in infancy and adulthood

Milo Taylor et al.

Summary: Using a rodent model, this study examined the short- and long-term effects of prolonged morphine administration in infancy on body weight and brain volume, as well as the brain vulnerability to subsequent exposure in adulthood. The results showed that prolonged morphine treatment in infancy led to lower body weight and smaller brain volumes, with no difference between sexes. However, prolonged morphine administration in adulthood was associated with smaller brain volumes, particularly in females with previous exposure in infancy.

FRONTIERS IN PAIN RESEARCH (2023)

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Article Chemistry, Medicinal

Synthesis, biological, and structural explorations of a series of μ-opioid receptor (MOR) agonists with high G protein signaling bias

Yifei Yang et al.

Summary: Biased agonism refers to compounds' ability to preferentially activate certain signaling pathways and avoid adverse signaling pathways in a ligand-dependent manner for some G-protein-coupled receptors. In this study, a series of derivatives with potent highly biased MOR agonism were rationally designed and synthesized through modification and structure-activity relationship study of TRV130. The novel molecule LPM3480392 demonstrated improved in vitro biased agonism, good brain penetration, and produced potent antinociceptive effect with reduced respiratory suppression compared to TRV130.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

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Review Anesthesiology

Oliceridine- Opioid of the 21st Century

Basavana Goudra

Summary: Oliceridine is an innovative opioid approved for clinical use in the United States. It aims to mitigate the side effects associated with opioids while maintaining its analgesic activity through a unique mechanism of action. However, further observations are needed to evaluate its effectiveness and safety in large-scale clinical use.

SAUDI JOURNAL OF ANAESTHESIA (2022)

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Article Neurosciences

Effect of TRV130 and methadone on fentanyl-vs.-food choice and somatic withdrawal signs in opioid-dependent and post-opioid-dependent rats

E. Andrew Townsend et al.

Summary: This study compared the effects of methadone with the intermediate efficacy MOR agonist TRV130 on fentanyl-vs.-food choice and somatic withdrawal signs in opioid-dependent and post-opioid-dependent rats. The results showed that TRV130 was less effective than methadone in reducing fentanyl choice in opioid-dependent rats, but it did not precipitate withdrawal in these rats.

NEUROPSYCHOPHARMACOLOGY (2022)

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Article Biochemistry & Molecular Biology

Molecular recognition of morphine and fentanyl by the human μ-opioid receptor

Youwen Zhuang et al.

Summary: This study reports the structural differences in the binding of morphine and fentanyl to the human mu-opioid receptor (mu OR), as well as the preferential interactions of other agonists with specific regions of the receptor. Mutations at certain regions abolish the recruitment of arrestin by morphine and fentanyl. Ligands designed to reduce interactions with specific regions display preferential G protein signaling. These findings provide crucial insights into the recognition and signaling of fentanyl, which could aid in the rational design of next-generation analgesics.

CELL (2022)

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Article Behavioral Sciences

Effects of the selective dopamine D3 receptor antagonist PG01037 on morphine-induced hyperactivity and antinociception in mice

Christian A. Botz-Zapp et al.

Summary: This study found that pretreatment with PG01037 can attenuate the hyperactivity and analgesic effects induced by morphine without affecting basal activity or pain sensitivity, but does not prevent the enhancement of locomotor sensitization following repeated morphine administration. Moreover, PG01037 does not induce catalepsy either alone or in combination with morphine. These results suggest that attenuation of acute opioid-induced hyperactivity may be a shared behavioral effect among D3R-selective antagonists, supporting further research into their potential use for opioid use disorder treatment. However, PG01037 differs from newer, highly-selective D3R antagonists in its ability to reduce opioid-induced analgesia, indicating that the modulation of opioid analgesia may vary across different D3R antagonists.

BEHAVIOURAL BRAIN RESEARCH (2021)

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Article Public, Environmental & Occupational Health

Trends and Geographic Patterns in Drug and Synthetic Opioid Overdose Deaths - United States, 2013-2019

Christine L. Mattson et al.

MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT (2021)

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Article Substance Abuse

Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the dorsomedial prefrontal cortex of male and female rats

Shirelle X. Liu et al.

Summary: Repeated morphine exposure induces changes in neural activity and gene expression in male and female rats, leading to behavioral abnormalities. The majority of differentially expressed genes are involved in synaptic signaling and neuroplasticity, with commonalities and some differences observed between sexes.

DRUG AND ALCOHOL DEPENDENCE (2021)

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Review Clinical Neurology

Oliceridine: A Novel Drug for the Management of Moderate to Severe Acute Pain - A Review of Current Evidence

Hon Sen Tan et al.

Summary: Oliceridine, a biased opioid agonist, activates G-protein signaling to reduce the risk of adverse effects compared to conventional opioids, but further studies are needed to confirm its safety profile and advantages.

JOURNAL OF PAIN RESEARCH (2021)

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Review Anesthesiology

The Effects of Anesthetics and Perioperative Medications on Immune Function: A Narrative Review

Robert S. Ackerman et al.

Summary: This review explores the intricate relationship between anesthetic agents, perioperative adjuvant medications, and immune function, highlighting the need for further research to understand the clinical implications and develop patient-specific strategies to enhance surgical outcomes.

ANESTHESIA AND ANALGESIA (2021)

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Article Biochemistry & Molecular Biology

Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats

Alok K. Paul et al.

Summary: The clinical use of morphine is limited by its side effects and the need for increasing doses to achieve adequate analgesia due to tolerance. High-dose morphine exposure leads to excitatory locomotor effects in animals, which later converts into an inhibitory effect on behavior.

MOLECULES (2021)

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Article Neurosciences