Investigating the potential of mirtazapine to induce drug-seeking behavior in free-choice drinking mouse model

Althobaiti, Yusuf S.

doi:10.1016/j.jsps.2022.10.010

Cited by 3 publications

(2 citation statements)

References 59 publications

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“…Many drugs used in the treatment of chronic pain show highly problematic central side effects including sedation, confusion, and memory problems (67, 68). Unlike opioids (67) and gabapentinoids (68), mPD5 did not significantly affect novelty induced exploration, general locomotor activity, or memory and learning. For opioids in particular there is a high risk of substance abuse (69) but abuse liability of gabapentinoids is also gaining attention (44).…”

Section: Discussionmentioning

confidence: 99%

mPD5, a peripherally restricted PICK1 inhibitor for treating chronic pain

Jensen,

Chistensen,

Goddard

et al. 2023

Preprint

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Chronic pain is a complex, debilitating, and escalating health problem worldwide, impacting one in five adults. Current treatment is compromised by dose-limiting side effects including high abuse liability, loss of ability to function socially and professionally, fatigue, drowsiness, and apathy. PICK1 has emerged as a promising target for the treatment of chronic pain conditions. Here, we develop and characterize a cell-permeable fatty acid conjugated bivalent peptide inhibitor of PICK1 and assess its effects on acute and chronic pain. The myristoylated myr-NPEG4-(HWLKV)2, (mPD5), self-assembles into core-shell micelles that provide favourable pharmacodynamic properties and relieves ongoing and evoked mechanical hypersensitivity, thermal hypersensitivity as well as anxio-depressive symptoms in mouse models of neuropathic and inflammatory pain following subcutaneous administration. No overt no side effects were associated with mPD5 administration, and it has no effect on acute nociception. Finally, neuropathic pain is relieved far into the chronic phase (18 weeks post SNI surgery) and while the effect of a single injection ceases after a few hours, repeated administration provides pain relief lasting up to 20 hours after the last injection.

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Section: Discussionmentioning

confidence: 99%

mPD5, a peripherally restricted PICK1 inhibitor for treating chronic pain

Jensen,

Chistensen,

Goddard

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Weight changes of bottles were recorded every 24 h to the nearest 0.1 g. Four identical pairs of bottles were positioned on vacant cages, a blank value had been established by subtracting the weight loss attributed to evaporation or leakage from weight change of bottle. Drug preference (%) was determined by dividing the volume of pregabalin intake by the total fluid intake (pregabalin solution + water) and multiplying the result by 100 ( Jaworski et al, 2005 , Althobaiti, 2022 ).…”

Section: Methodsmentioning

confidence: 99%