Toward directing opioid receptor signaling to refine opioid therapeutics

TW Grim, A Acevedo-Canabal, LM Bohn - Biological psychiatry, 2020 - Elsevier
The mu opioid receptor (MOR) is a diversely regulated target for the alleviation of pain in the
clinical setting. However, untoward side effects such as tolerance, dependence, respiratory …

[HTML][HTML] Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity

M Soethoudt, U Grether, J Fingerle, TW Grim… - Nature …, 2017 - nature.com
The cannabinoid CB 2 receptor (CB 2 R) represents a promising therapeutic target for various
forms of tissue injury and inflammatory diseases. Although numerous compounds have …

[PDF][PDF] Activation and signaling mechanism revealed by cannabinoid receptor-Gi complex structures

…, X Song, S Yuan, Q Sun, Y Wu, S Jiang, TW Grim… - Cell, 2020 - cell.com
Human endocannabinoid systems modulate multiple physiological processes mainly through
the activation of cannabinoid receptors CB1 and CB2. Their high sequence similarity, low …

AG protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine withdrawal

TW Grim, CL Schmid, EL Stahl, F Pantouli… - …, 2020 - nature.com
It has been demonstrated that opioid agonists that preferentially act at μ-opioid receptors to
activate G protein signaling over βarrestin2 recruitment produce antinociception with less …

G protein signaling–biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists

…, C Read, TW Grim… - Proceedings of the …, 2021 - National Acad Sciences
The ability of a ligand to preferentially promote engagement of one signaling pathway over
another downstream of GPCR activation has been referred to as signaling bias, functional …

The selective monoacylglycerol lipase inhibitor MJN110 produces opioid-sparing effects in a mouse neuropathic pain model

JL Wilkerson, MJ Niphakis, TW Grim, MA Mustafa… - … of Pharmacology and …, 2016 - ASPET
Serious clinical liabilities associated with the prescription of opiates for pain control include
constipation, respiratory depression, pruritus, tolerance, abuse, and addiction. A recognized …

Effectiveness comparisons of G-protein biased and unbiased mu opioid receptor ligands in warm water tail-withdrawal and drug discrimination in male and female rats

…, KC Rice, S Obeng, Y Zhang, BE Blough, TW Grim… - …, 2019 - Elsevier
One emerging strategy to address the opioid crisis is the development of mu opioid receptor
(MOR) ligands that preferentially signal the G-protein vs. β-arrestin pathway. The present …

Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in mouse neuropathic and inflammatory pain models

TW Grim, S Ghosh, KL Hsu, BF Cravatt… - Pharmacology …, 2014 - Elsevier
Common pharmacological treatments of neuropathic and chronic inflammatory pain
conditions generally lack efficacy and/or are associated with significant untoward side effects. …

Δ9-tetrahydrocannabinol and endocannabinoid degradative enzyme inhibitors attenuate intracranial self-stimulation in mice

JM Wiebelhaus, TW Grim, RA Owens… - … of Pharmacology and …, 2015 - ASPET
A growing body of evidence implicates endogenous cannabinoids as modulators of the
mesolimbic dopamine system and motivated behavior. Paradoxically, the reinforcing effects of Δ …

Full fatty acid amide hydrolase inhibition combined with partial monoacylglycerol lipase inhibition: augmented and sustained antinociceptive effects with reduced …

…, Q Liu, L Hruba, LR McMahon, TW Grim… - … of Pharmacology and …, 2015 - ASPET
Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the primary
hydrolytic enzymes for the respective endocannabinoids N-arachidonoylethanolamine (…