A5010714266- Cannabis and Cannabinoid Research
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Neurotransmitter Receptor Influence on Behavior
- Pain Mechanisms and Treatments
- Ion channel regulation and function
- Forensic Toxicology and Drug Analysis
- Ion Channels and Receptors
- Nicotinic Acetylcholine Receptors Study
- Neuroscience of respiration and sleep
- Psychedelics and Drug Studies
- Neuroendocrine regulation and behavior
- Insect and Pesticide Research
- Biochemical Analysis and Sensing Techniques
- Electrolyte and hormonal disorders
- Cancer, Stress, Anesthesia, and Immune Response
- Venomous Animal Envenomation and Studies
- Pharmacological Effects and Assays
- Migraine and Headache Studies
- Advanced biosensing and bioanalysis techniques
- Herbal Medicine Research Studies
- Sleep and Wakefulness Research
- Marine Toxins and Detection Methods
Macquarie University
2016-2025
Australian Research Council
2025
Institute of Environmental Science and Research
2024
The University of Sydney
2003-2012
MIND Research Institute
2012
Royal North Shore Hospital
2004-2011
University of British Columbia
2010
Assembly of First Nations
2010
University of Nottingham
2009
North Shore Hospital
2006
Biased agonism at G protein-coupled receptors describes the phenomenon whereby some drugs can activate downstream signaling activities to relative exclusion of others. Descriptions biased focusing on differential engagement proteins versus β-arrestins are commonly limited by small response windows obtained in pathways that not amplified or less effectively coupled receptor engagement, such as β-arrestin recruitment. At μ-opioid (MOR), protein-biased ligands have been proposed induce...
Abstract The cannabinoid CB 2 receptor (CB R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed widely used to R, their selectivity, molecular mode action pharmacokinetic properties poorly characterized. Here we report the most extensive characterization pharmacology R ligands date. In collaborative effort between multiple academic industry laboratories, identify marked differences in...
Indole and indazole synthetic cannabinoids (SCs) featuring l-valinate or l-tert-leucinate pendant group have recently emerged as prevalent recreational drugs, their use has been associated with serious adverse health effects. Due to the limited pharmacological data available for these compounds, 5F-AMBICA, 5F-AMB, 5F-ADB, AMB-FUBINACA, MDMB-FUBINACA, MDMB-CHMICA, analogues were synthesized assessed cannabimimetic activity in vitro vivo. All SCs acted potent, highly efficacious agonists at...
Synthetic cannabinoid (SC) designer drugs based on indole and indazole scaffolds featuring l-valinamide or l-tert-leucinamide side chains are encountered with increasing frequency by forensic researchers law enforcement agencies associated serious adverse health effects. However, many of these novel SCs unprecedented in the scientific literature at time their discovery, little is known pharmacology. Here, we report synthesis pharmacological characterization AB-FUBINACA, ADB-FUBINACA,...
Synthetic cannabinoid (SC) designer drugs featuring bioisosteric fluorine substitution are identified by forensic chemists and toxicologists with increasing frequency. Although terminal fluorination of N-pentyl indole SCs is sometimes known to improve type 1 (CB1) receptor binding affinity, little the effects on functional activity SCs. This study explores in vitro activities SC JWH-018, UR-144, PB-22, APICA, their respective terminally fluorinated analogues AM-2201, XLR-11, 5F-PB-22,...
The midbrain periaqueductal gray (PAG) is a major site of cannabinoid-mediated analgesia in the central nervous system. In present study, we examined actions cannabinoids on rat PAG neurons vitro. brain slices, superfusion cannabinoid receptor agonist WIN55,212-2 inhibited electrically evoked inhibitory and excitatory postsynaptic currents all neurons. endogenous anandamide presence transport inhibitor AM404, but not its absence. stable analog R1-methanandamide also currents. reduced rate...
In this study we have examined the effects of nociceptin, an endogenous ligand for opioid‐like receptor ORL 1 , on membrane properties rat locus coeruleus (LC) neurones in vitro using intracellular and whole cell patch clamp recording. When were voltage clamped to −60 mV, application nociceptin caused outward current all cells ( n = 49), with EC 50 90 nM. Neither potency nor maximal effect was altered presence peptidase inhibitors, bestatin (20 μ m ) or thiorphan (2 ). The currents by 2.5 mM...
Gingerols, the pungent constituents of ginger, were synthesized and assessed as agonists capsaicin‐activated VR1 (vanilloid) receptor. [6]‐Gingerol [8]‐gingerol evoked capsaicin‐like intracellular Ca 2+ transients ion currents in cultured DRG neurones. These effects gingerols blocked by capsazepine, receptor antagonist. The potency increased with increasing size side chain overall hydrophobicity series. We conclude that represent a novel class naturally occurring may contribute to medicinal...
The human neuroblastoma cell line SH‐SY5Y expresses the ‘orphan’ opioid receptor (ORL1). We have demonstrated that nociceptin, putative endogenous ligand for ORL1, produces a concentration‐dependent inhibition of N‐type calcium channel current in these cells (IC 50 42 nM). In addition, presence carbachol, nociceptin increased intracellular concentration Ca 2+ (EC 60 Both effects were blocked by pertussis toxin pretreatment but not antagonists CTAP (1 μ m ), naltrindole ) and naloxone (10 ).
Delta(9)-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prevalent biologically active constituents of Cannabis sativa. THC is prototypic cannabinoid CB1 receptor agonist psychoactive analgesic. CBD also analgesic, but it not a agonist. Low voltage-activated T-type calcium channels, encoded by Ca(V)3 gene family, regulate excitability many cells, including neurons involved in nociceptive processing. We examined effects on human channels stably expressed embryonic kidney 293...
The cannabinoid receptor type 1 (CB1 ) has an allosteric binding site. drugs ORG27569 {5-chloro-3-ethyl-N-[2-[4-(1-piperidinyl)phenyl]ethyl]-1H-indole-2-carboxamide} and PSNCBAM-1 {1-(4-chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea} have been extensively characterized with regard to their effects on signalling of the orthosteric ligand CP55,940 {(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol}, studies suggested that these modulators...
Introduction: Compounds present in Cannabis sativa such as phytocannabinoids and terpenoids may act concert to elicit therapeutic effects. Cannabinoids Δ9-tetrahydrocannabinol (Δ9-THC) directly activate cannabinoid receptor 1 (CB1) 2 (CB2); however, it is not known if also affect signaling. Therefore, we examined six common alone, combination with agonists, on CB1 CB2 signaling vitro. Materials Methods: Potassium channel activity AtT20 FlpIn cells transfected human or receptors was measured...
Background and Purpose Cannabichromene (CBC) is one of the most abundant phytocannabinoids in Cannabis spp . It has modest antinociceptive anti‐inflammatory effects potentiates some Δ 9 ‐tetrahydrocannabinol vivo. How CBC exerts these poorly defined there little information about its efficacy at cannabinoid receptors. We sought to determine functional activity CB 1 2 Experimental Approach AtT20 cells stably expressing haemagglutinin‐tagged human receptors were used. Assays cellular membrane...
Chronic morphine administration induces adaptations in neurons resulting opioid tolerance and dependence. Functional studies have implicated a role for the periaqueductal gray area (PAG) expression of many signs withdrawal, but cellular mechanisms are not fully understood. This study describes an increased efficacy, rather than tolerance, agonists at μ-receptors on GABAergic (but glutamatergic) nerve terminals PAG after chronic treatment. Opioid withdrawal enhanced amplitudes electrically...
The differential ability of various mu-opioid receptor (MOP) agonists to induce rapid desensitization and endocytosis MOP could arise simply from differences in their efficacy activate G proteins or, alternatively, be due capacity for activation other signaling processes. We used AtT20 cells stably expressing a low density FLAG-tagged compare the efficacies range 1) using inhibition calcium channel currents (ICa) as reporter before after inactivation fraction receptors by...
The vanilloid receptor protein (VR1) is a well-characterised integrator of noxious stimuli in peripheral sensory neurones. There evidence for the presence VR1 central nervous system, but little information as to its role there. In this study we have examined actions agonists receptors rat locus coeruleus (LC), using whole-cell patch-clamp recordings from acutely isolated neurones and slices. Superfusion with capsaicin resulted concentration-dependent increase frequency miniature excitatory...