All Outputs (45)

Assessment of the potential of novel and classical opioids to induce respiratory depression in mice (2023)
Journal Article

Background and Purpose Opioid-induced respiratory depression limits the use of μ-opioid receptor agonists in clinical settings and is the main cause of opioid overdose fatalities. The relative potential of different opioid agonists to induce respira... Read More about Assessment of the potential of novel and classical opioids to induce respiratory depression in mice.

OZITX, A pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz (2022)
Journal Article

Heterotrimeric G proteins are the main signalling effectors for G protein-coupled receptors. Understanding the distinct functions of different G proteins is key to understanding how their signalling modulates physiological responses. Pertussis toxin,... Read More about OZITX, A pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz.

The respiratory depressant effects of mitragynine are limited by its conversion to 7-OH mitragynine (2022)
Journal Article

Background and Purpose: Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), is a partial agonist at the μ opioid receptor. CYP3A-dependent oxidation of mitragynine yields the metabolite 7-OH mitragynine, a more efficacious μ receptor agon... Read More about The respiratory depressant effects of mitragynine are limited by its conversion to 7-OH mitragynine.

Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10 (2021)
Journal Article

Chemokines interact with chemokine receptors in a promiscuous network, such that each receptor can be activated by multiple chemokines. Moreover, different chemokines have been reported to preferentially activate different signalling pathways via the... Read More about Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10.

New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine D2 receptor regulation and signaling (2021)
Journal Article

The dopamine D2 receptor (D2R) is the target of drugs used to treat the symptoms of Parkinson’s disease and schizophrenia. The D2R is regulated through its interaction with and phosphorylation by G protein receptor kinases (GRKs) and interaction with... Read More about New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine D2 receptor regulation and signaling.

GRKs as Key Modulators of Opioid Receptor Function (2020)
Journal Article

Understanding the link between agonist-induced phosphorylation of the mu-opioid receptor (MOR) and the associated physiological effects is critical for the development of novel analgesic drugs and is particularly important for understanding the mecha... Read More about GRKs as Key Modulators of Opioid Receptor Function.

Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism (2020)
Journal Article

By analyzing and simulating inactive conformations of the highly-homologous dopamine D2 and D3 receptors (D2R and D3R), we find that eticlopride binds D2R in a pose very similar to that in the D3R/eticlopride structure but incompatible with the D2R/r... Read More about Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism.

Structure-Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D2 Receptor (2019)
Journal Article

Haloperidol is a typical antipsychotic drug (APD) associated with an increased risk of extrapyramidal side-effects (EPS) and hyperprolactinemia relative to atypical APDs such as clozapine. Both drugs are dopamine D2 receptor (D2R) antagonists, with c... Read More about Structure-Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D2 Receptor.

Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole (2019)
Journal Article

Partial agonists of the dopamine D2 receptor (D2R) have been developed to treat the symptoms of schizophrenia without causing the side effects elicited by antagonists. The receptor-ligand interactions that determine the intrinsic efficacy of such dru... Read More about Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole.

Arrestin recruitment to dopamine D2 receptor mediates locomotion but not incentive motivation (2018)
Journal Article

The dopamine (DA) D2 receptor (D2R) is an important target for the treatment of neuropsychiatric disorders such as schizophrenia and Parkinson's disease. However, the development of improved therapeutic strategies has been hampered by our incomplete... Read More about Arrestin recruitment to dopamine D2 receptor mediates locomotion but not incentive motivation.

Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-(( trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor (2018)
Journal Article

SB269652 (1) is a negative allosteric modulator of the dopamine D2 receptor. Herein, we present the design, synthesis, and pharmacological evaluation of "second generation" analogues of 1 whereby subtle modifications to the indole-2-carboxamide motif... Read More about Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-(( trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor.

The action of a negative allosteric modulator at the dopamine D2 receptor is dependent upon sodium ions (2018)
Journal Article

© 2018 The Author(s). Sodiumions (Na+) allosterically modulate the binding of orthosteric agonists and antagonists to many class A G protein-coupled receptors, including the dopamine D 2 receptor (D 2 R). Experimental and computational evidences have... Read More about The action of a negative allosteric modulator at the dopamine D2 receptor is dependent upon sodium ions.

The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2 and D3 receptors (2018)
Journal Article

The dopamine D2 and D3 receptors (D2R and D3R) are important targets for antipsychotics and for the treatment of drug abuse. SB269652, a bitopic ligand that simultaneously binds both the orthosteric binding site (OBS) and a secondary binding pocket (... Read More about The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2 and D3 receptors.

Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors (2017)
Journal Article

Atypical antipsychotic drugs (APDs) have been hypothesized to show reduced extrapyramidal side effects (EPS) due to their rapid dissociation from the dopamine D2 receptor. However, support for this hypothesis is limited to a relatively small number o... Read More about Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors.

Multivalent approaches and beyond: novel tools for the investigation of dopamine D2 receptor pharmacology (2016)
Journal Article

The dopamine D2 receptor (D2R) has been implicated in the symptomology of disorders such as schizophrenia and Parkinson's disease. Multivalent ligands provide useful tools to investigate emerging concepts of G protein-coupled receptor drug action suc... Read More about Multivalent approaches and beyond: novel tools for the investigation of dopamine D2 receptor pharmacology.

?2-Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer (2016)
Journal Article

© 2016 The Authors Chronic stress accelerates metastasis – the main cause of death in cancer patients – through the activation of β-adrenoceptors (βARs). We have previously shown that β2AR signaling in MDA-MB-231HM breast cancer cells, facilitates in... Read More about ?2-Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer.

The role of kinetic context in apparent biased agonism at GPCRs (2016)
Journal Article

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usu... Read More about The role of kinetic context in apparent biased agonism at GPCRs.

4-Phenylpyridin-2-one Derivatives: A Novel Class of Positive Allosteric Modulator of the M1 Muscarinic Acetylcholine Receptor (2015)
Journal Article

Positive allosteric modulators (PAMs) of the M1 muscarinic acetylcholine receptor (M1 mAChR) are a promising strategy for the treatment of the cognitive deficits associated with diseases including Alzheimer’s and schizophrenia. Herein, we report the... Read More about 4-Phenylpyridin-2-one Derivatives: A Novel Class of Positive Allosteric Modulator of the M1 Muscarinic Acetylcholine Receptor.

?2-adrenoceptor signaling regulates invadopodia formation to enhance tumor cell invasion (2015)
Journal Article

INTRODUCTION:For efficient metastatic dissemination, tumor cells form invadopodia to degrade and move through three-dimensional extracellular matrix. However, little is known about the conditions that favor invadopodia formation. Here, we investigate... Read More about ?2-adrenoceptor signaling regulates invadopodia formation to enhance tumor cell invasion.

The ?2?adrenoceptor activates a positive cAMP?calcium feedforward loop to drive breast cancer cell invasion (2015)
Journal Article