A5065769580- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Cannabis and Cannabinoid Research
- Neuropeptides and Animal Physiology
- Forensic Toxicology and Drug Analysis
- Pharmacological Receptor Mechanisms and Effects
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Psychedelics and Drug Studies
- Bipolar Disorder and Treatment
- Phosphodiesterase function and regulation
- Pharmacological Effects and Toxicity Studies
- Attention Deficit Hyperactivity Disorder
- Treatment of Major Depression
- Sleep and Wakefulness Research
- Pain Mechanisms and Treatments
- Drug Transport and Resistance Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Epilepsy research and treatment
- Diet and metabolism studies
- Synthesis and Biological Evaluation
- Radiopharmaceutical Chemistry and Applications
- Chemical synthesis and alkaloids
- Neurological disorders and treatments
VA Portland Health Care System
2016-2024
Oregon Health & Science University
2015-2024
CoDa Therapeutics (United States)
2019-2020
Pennsylvania State University
2018
Jazz Pharmaceuticals (United States)
2018
University of North Texas
2018
University of North Texas Health Science Center
2018
University of Arkansas for Medical Sciences
2018
National Institutes of Health
1984-2016
Portland VA Medical Center
2002-2016
Small conductance Ca(2+)-activated potassium channels (SK channels) are coassembled complexes of pore-forming SK alpha subunits and calmodulin. We proposed a model for channel activation in which Ca2+ binding to calmodulin induces conformational rearrangements the that result gating. now report fluorescence measurements indicate changes subunit after subunit-calmodulin complex. Two-hybrid experiments showed Ca(2+)-independent interaction with requires only C-terminal domain is mediated by...
We characterized the effects of drugs on uptake [3H]neurotransmitter by and binding [125I](3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester ([125I]RTI-55) to recombinant human dopamine (hDAT), serotonin (hSERT), or norepinephrine (hNET) transporters stably expressed in embryonic kidney 293 cells. RTI-55 had similar affinity for hDAT hSERT lower hNET (Kd = 1. 83, 0.98, 12.1 nM, respectively). Kinetic analysis [125I]RTI-55 indicated that dissociation rate (k-1) was significantly...
The action of desipramine on the norepinephrine-sensitive adenylate cyclase system and density beta-adrenergic receptors in rat cortex was studied after selective lesioning serotonergic neurons with 5,7-dihydroxytryptamine. In animals lesions failed to reduce beta-adrenoceptors but decreased response adenosine 3',5'-monophosphate isoproterenol norepinephrine same degree as without lesions. results demonstrate a functional linkage between noradrenergic systems cortex, neurohormonal...
High-affinity and saturable binding sites for the diphenyl-substituted piperazine derivative [3H]GBR-12935 have been characterized in crude synaptosomal membranes prepared from rat brain. The specific of is sodium-dependent unevenly distributed among various brain regions, with highest concentration being found corpus striatum nucleus accumbens. Sodium-dependent all other areas was 10% or less striatum. affinity increased presence Na+ but cations, including K+, Ca2+, Mg2+, inhibit binding....
Abstract: Saturable and stereoselective binding sites for [ 3 H]threo‐(±)‐methylphenidate were characterized in rat brain membranes. The highest density of H]threo‐(±)‐ methylphenidate was found the synapto somal fraction corpus striatum. Scatchard analysis revealed a single class noninteracting with an apparent dissociation constant ( K D ) 235 n M maximum number B max 13.4 pmol/mg protein. Saturable, high‐affinity to striatal synaptosomal membranes dependent on presence sodium ions. A good...
Synthetic cathinones are components of “bath salts” and have physical psychologic side effects, including hypertension, paranoia, hallucinations. Here, we report interactions 20 salt” with human dopamine, serotonin, norepinephrine transporters [human dopamine transporter (hDAT), serotonin (hSERT), (hNET), respectively] heterologously expressed in embryonic kidney 293 cells. Transporter inhibitors had nanomolar to micromolar affinities (K<sub>i</sub> values) at radioligand binding sites,...
The benzimidazole opioids (substituted nitazenes) are highly potent μ opiod receptor (MOR) agonists with heroin- or fentanyl-like effects. These compounds have caused hospitalizations and fatal overdoses. We characterized the in vitro pharmacology structure-activity relationships of 19 nitazenes substitutions at three positions core. Affinities were assessed using agonist radioligand binding assays human μ, κ, Δ opioid receptors (MOR, KOR, DOR, respectively) heterologously expressed CHO...
A human dopamine transporter cDNA was cloned and transfected into COS-7 cells, a cell line that lacks vesicular storage release mechanisms. Cells expressing the acquired capacity to take up via transporter. Ionic conditions stimulate inside-out transport in vivo, such as depolarizing concentrations of K+ or low extracellular Na+, were found Ca(2+)-independent [3H]dopamine from cells. Dopamine uptake inhibitors had one three effects on transporter-mediated efflux. Some drugs, addition...
Excessive sleepiness (ES) is associated with several sleep disorders, including narcolepsy and obstructive apnea (OSA). A role for monoaminergic systems in treating these conditions highlighted by the clinical use of US Food Drug Administration–approved drugs that act on systems, such as dextroamphetamine, methylphenidate, modafinil, armodafinil. Solriamfetol (JZP-110) a wake-promoting agent currently being evaluated to treat ES patients or OSA. Clinical preclinical data suggest effects...
Synthetic opioids, including fentanyl and its analogs, have therapeutic efficacy in analgesia anesthesia. However, their illicit use the United States has increased contributed to number one cause of death for adults 18–50 years old. Fentanyl heroin metabolite morphine induce respiratory depression that can be treated with <i>μ</i> opioid receptor (MOR) antagonist naloxone. With higher or more rapid dosing, fentanyl, than morphine, causes chest wall rigidity also onset laryngospasm. Because...
In response to a surge of deaths from synthetic opioid overdoses, there have been increased efforts distribute naloxone products in community settings. Prior research has assessed the effectiveness hospital setting; however, it is challenging assess dosing regimens community/first-responder setting, including reversal respiratory depression effects fentanyl and its derivatives (fentanyls). Here, we describe development validation mechanistic model that combines mu receptor binding kinetics,...
Novel psychoactive substances, including synthetic substituted tryptamines, represent a potential public health threat. Additionally, some tryptamines are being studied under medical guidance as treatments of psychiatric disorders. Characterizing the basic pharmacology will aid in understanding differences for harm or therapeutic use. Using human embryonic kidney cells stably expressing 5-hydroxytryptamine (5-HT)
The existence of two molecular forms D2 dopamine receptors suggests that differences in the distribution or regulation could be exploited for pharmacological treatment disease. Using probes selective each alternatively spliced variant receptor mRNA, we determined both variants were widely distributed rat brain and pituitary but ratio varied among regions. mRNA 444-amino acid-long variant, D2(444), was most abundant form neostriatum. Intermediate levels D2(444) short form, D2(415), detected...