A5086682653- Cannabis and Cannabinoid Research
- Pain Mechanisms and Treatments
- Alkaloids: synthesis and pharmacology
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Traditional and Medicinal Uses of Annonaceae
- Chemical synthesis and alkaloids
- Neurotransmitter Receptor Influence on Behavior
- Nerve injury and regeneration
- Molecular spectroscopy and chirality
- Sleep and Wakefulness Research
- Ion channel regulation and function
- Hereditary Neurological Disorders
- Biochemical effects in animals
- Axial and Atropisomeric Chirality Synthesis
- Berberine and alkaloids research
- Cancer Treatment and Pharmacology
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Smoking Behavior and Cessation
- Migraine and Headache Studies
- Forensic Toxicology and Drug Analysis
- Neuropeptides and Animal Physiology
- Pharmacological Effects of Natural Compounds
University of Florida
2019-2024
Texas Tech University Health Sciences Center
2022-2024
Texas Tech University
2022-2024
Samford University
2022-2023
National Institute on Drug Abuse
2020-2023
National Institutes of Health
2020-2023
University of South Carolina
2022-2023
The University of Texas at San Antonio
2022
The University of Texas Health Science Center at San Antonio
2022
Louisiana State University
2022
Relationships between <i>µ</i>-opioid receptor (MOR) efficacy and effects of mitragynine 7-hydroxymitragynine are not fully established. We assessed in vitro binding affinity discriminative stimulus together with antinociception rats. The affinities at MOR (K<sub>i</sub> values 77.9 709 nM, respectively) were higher than their <i>κ</i>-opioid (KOR) or <i>δ</i>-opioid (DOR). [<sup>35</sup>S]guanosine 5′-<i>O</i>-[<i>γ</i>-thio]triphosphate stimulation demonstrated that was an antagonist,...
Summary Spinal AM1710 suppresses allodynia with corresponding anti-inflammatory and anti-MAGL (monoacylglycerol lipase) effects in the spinal cord dorsal root ganglia. glial proinflammatory cytokine actions are strongly implicated pathological pain. administration of interleukin (IL)-10 abolishes pain IL-1β tumor necrosis factor alpha (TNF-α). Drugs that bind cannabinoid type-2 receptor (CB2R) expressed on glia reduce mechanical hypersensitivity. To better understand CB2R-related profile key...
Amorphous mesoporous silica nanoparticles ('protocells') that support surface lipid bilayers recently characterized in vitro as carrier constructs for small drug and DNA delivery are reported here highly biocompatible both vivo, involving the brain spinal cord following into lumbosacral subarachnoid space (intrathecal; i.t.). Specifically, positively charged, 1, 2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP)–cholesterol (DOTAP:Chol) liposome-formulated protocells revealed stable cargo...
The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) plays an important role in a variety of physiologic processes, but its rapid breakdown by monoacylglycerol lipase (MAGL) results short-lived actions. Initial MAGL inhibitors were limited poor selectivity and low potency. In this study, we tested JZL184 [4-nitrophenyl 4-[bis(2<i>H</i>-1,3-benzodioxol-5-yl)(hydroxy)methyl]piperidine-1-carboxylate] MJN110 [2,5-dioxopyrrolidin-1-yl 4-(bis(4-chlorophenyl)methyl)piperazine-1-carboxylate],...
Although paclitaxel effectively treats various cancers, its debilitating peripheral neuropathic pain side effects often persist long after treatment has ended. Therefore, a compelling need exists for the identification of novel pharmacologic strategies to mitigate this condition. As inhibitors monoacylglycerol lipase (MAGL), primary hydrolytic enzyme endogenous cannabinoid, 2-arachidonyolglycerol, produces antinociceptive in numerous rodent models pain, we investigated whether (i.e., JZL184...
Here, we have characterized 3-cyclopropyl-1-(4-(6-((1,1-dioxidothiomorpholino)methyl)-5-fluoropyridin-2-yl)benzyl)imidazolidine-2,4-dione hydrochloride (LEI-101) as a novel, peripherally restricted cannabinoid CB2 receptor agonist, using both in vitro and vivo models.
Orthosteric agonists and positive allosteric modulators (PAMs) of the α7 nicotinic ACh receptor (nAChR) represent novel therapeutic approaches for pain modulation. Moreover, compounds with dual function as PAMs, known ago-PAMs, add further regulation function.Initial studies examined ago-PAM, GAT107, in formalin, complete Freund's adjuvant (CFA), LPS inflammatory models, chronic constriction injury neuropathic model tail flick hot plate acute thermal nociceptive assays. Additional locus...
Serious clinical liabilities associated with the prescription of opiates for pain control include constipation, respiratory depression, pruritus, tolerance, abuse, and addiction. A recognized strategy to circumvent these side effects is combine opioids other antinociceptive agents. The combination primary active constituent cannabis (Δ<sup>9</sup>-tetrahydrocannabinol) produces enhanced actions, suggesting that cannabinoid receptor agonists can be opioid sparing. Here, we tested whether...
The individual and global burden of migraine is such significance that there are accelerated efforts to develop new therapies. New therapeutics needed address the current deficiencies exist in efficacy adherence rate approved anti-migraine medications. recent discovery calcitonin gene related peptide as an add-on role serotonin has markedly increased range treatment options for acute chronic migraine. Despite this, tackling complexity disorders requires a complete understanding its...
Peri-spinal subarachnoid (intrathecal; i.t.) injection of non-viral naked plasmid DNA encoding the anti-inflammatory cytokine, IL-10 (pDNA-IL-10) suppresses chronic neuropathic pain in animal models. However, two sequential i.t. pDNA injections are required within a discrete 5 to 72-hour period for prolonged efficacy. Previous reports identified phagocytic immune cells present peri-spinal milieu surrounding i.t site that may play role transgene uptake resulting subsequent expression. In...
Abstract During pathological pain, the actions of endocannabinoid system, including cannabinoid 2 receptor (CB R), leads to effective anti‐allodynia and modifies a variety spinal microglial astrocyte responses. Here, following administration CB R compound, AM1241, we examined immunoreactive alterations in markers for activated p38 mitogen‐activated protein kinase, interleukin‐1β (IL‐1β), anti‐inflammatory cytokine, interleukin‐10 (IL‐10) as well degradative enzymes, altered glial responses...
Inhibition of diacylglycerol lipase (DGL)β prevents LPS-induced pro-inflammatory responses in mouse peritoneal macrophages. Thus, the present study tested whether DGLβ inhibition reverses allodynic mice LPS model inflammatory pain, as well neuropathic pain models.Initial experiments examined cellular expression and mediators within LPS-injected paw pad. DAGL-β (-/-) or wild-type treated with inhibitor KT109 were assessed pain. Additional studies locus action for KT109-induced...
Chemotherapy-induced peripheral neuropathy (CIPN) represents a serious complication associated with antineoplastic drugs. Although there are no medications available that effectively prevent CIPN, many classes of drugs have been used to treat this condition, including anticonvulsants, serotonin and noradrenaline reuptake inhibitors, opioids. However, these therapeutic options yielded inconclusive results in CIPN clinical trials produced assorted side effects their prolonged use. Thus, is an...
The primary kratom alkaloid mitragynine is proposed to act through multiple mechanisms, including actions at <i>µ</i>-opioid receptors (MORs) and adrenergic-<i>α</i><sub>2</sub> (A<i>α</i><sub>2</sub>Rs), as well conversion in vivo a MOR agonist metabolite (i.e., 7-hydroxymitragynine). A<i>α</i><sub>2</sub>R agonists can produce antinociceptive synergism. Here, contributions of both mitragynine-related effects were assessed by measuring receptor binding cell membranes and, rats,...