Jay McLaughlin

Jay McLaughlin, Ph.D.

Professor

Department: Pharmacodynamics
Business Phone: (352) 273-7207
Business Email: jpmclaughlin@ufl.edu

About Jay McLaughlin

Jay McLaughlin, Ph.D., joined the College of Pharmacy as an associate professor of pharmacodynamics and was promoted to professor in July 2020. Prior to joining UF, he worked at the Torrey Pines Institute for Molecular Studies in Port St. Lucie, Florida. His research goal is to identify the neurobiological systems underlying behavior, characterizing them and related psychological disorders to developing new therapeutic interventions utilizing molecular, pharmacological, anatomical and behavioral methods. His projects encompass both basic science and drug discovery elements.

Accomplishments

Team Teaching Award (PC6 ALS1)
2020 · University of Florida, College of Pharmacy
Term Professor
2019-2022 · University of Florida
Preeminence Faculty Member
2015-Current · University of Florida
Travel Fellowship
2008-2009 · International Narcotics Research Conference
Teaching Excellence Award
2007 · Northeastern University
Travel Fellowship
2006 · International Narcotics Research Conference
Travel Fellowship
2005 · International Narcotics Research Conference
Travel Fellowship
2001-2003 · International Narcotics Research Conference
NIDA Director’s Travel Award
1998 · College on Problems of Drug Dependence Meeting
Travel Fellowship
1998 · International Narcotics Research Conference
NIDA Director’s Travel Award
1995 · College on Problems of Drug Dependence Meeting
Travel Fellowship
1994 · International Narcotics Research Conference

Teaching Profile

Courses Taught
2017-2018,2020-2022
PHA5788C Patient Care 6
2016-2017,2019-2022
PHA6521C Research Techniques in Pharmacodynamics
2016-2023
PHA7980 Research for Doctoral Dissertation
2016-2020
PHA7979 Advanced Research
2016-2017,2020-2021
PHA6936 Advanced Topics in Pharmaceutical Sciences
2016-2023
PHA6512L Experiential Research Training in Pharmacodynamics
2019-2020
PHA6910 Supervised Research
2019-2021
PHA6935 Selected Topics in Pharmacy
2020
PHA6971 Research for Master’s Thesis
2016-2019
PHA5561 Pathphys-Pt Assess II
2017-2018
PHA4911 Undergraduate Research in Pharmacodynamics
2016
PHA5517 Pharmacol Bas Ther 2
2016
GMS7794 Neuroscience Seminar
2015
PHA5902 Research Pharmacodyna
2015
PHA5561C Physiol Bas Disease 2
2021
BSC4910 Individual Mentored Research in Biology

Research Profile

I am interested in questions examining the neurobiological basis of behavior, focusing on the molecular, pharmacological and neurological mechanisms underlying behavior and psychological disorders. While these interests are broad, my overall goal is to identify the neurobiological systems underlying these behaviors, characterize them, and develop new therapeutic interventions. Working towards this goal, I utilize molecular, chemical, pharmacological, anatomical and behavioral methodology. Ongoing projects include:

Mechanisms by which HIV mediates neuropathology and alters behavior. The widespread use of HAART therapies has curtailed the expression and spread of the Human Immunodeficiency Virus (Cohen et al., 2011), but these patients continue to display severe neuropathology and behavioral disorders that cannot be presently accounted for including deficits in motor coordination, learning and memory, behavioral inhibition, and affective well-being (Woods et al. 2009), a syndrome roughly defined as NeuroAIDS. The HIV regulatory protein, Tat, has been implicated in the pathogenesis of HIV-1 neurological complications (Rappaport et al., 1999), but direct demonstrations of the effects of Tat on behavior and neurodegeneration in an intact organism in vivo are limited. This project used for the first time a novel animal model, the GT-tg bigenic mouse. These mice contain a doxycycline (Dox)-inducible and brain-selective tat gene coding for Tat protein, allowing the controlled expression of Tat protein for selective study on desired pathological and behavioral questions. Accordingly, this project uses GT-tg bigenic mice to test the hypothesis that the activity of Tat in brain is sufficient to produce neuronal dysfunction and neurodegeneration producing behavioral deficits in learning and memory performance, mood disorders, and increases in drug seeking behaviors.

Mechanisms by which stress modulates reward and contributes to disorders of mood, drug abuse, learning and memory. This project has demonstrated that exposure to stress activates the endogenous kappa opioid system to potentiate reward and induce relapse to extinguished drug-seeking (cocaine and ethanol) behaviors, as well as increase depression-like behaviors.Additional work under this project has also demonstrated that endogenous kappa opioid activation mediates stress-induced deficits in learning and memory (Carey et al., J Neurosci. 29:4293-4300, 2009). Overall, these results suggest that stress-induced activation of the KOR may be both necessary and sufficient to produce subsequent deficits in novel object recognition, and suggest both new insights into the means by which stress impairs learning and memory performance, as well as therapeutic approaches for treating exposure to stress.Present findings suggest that novel kappa opioid agonists may be beneficial in the short term to prevent acute narcotic-induced reward, but that antagonists may be of additional benefit as treatments for drug relapse and antidepressants. We have demonstrated that kappa-opioid receptor stimulation is necessary and sufficient to produce the potentiation. Additionally, we have preliminary evidence demonstrating that earlier exposure to stress increases drug-seeking and depression-like behaviors for extended (weeks) periods in mice, an animal model of PTSD. Importantly, we have recently demonstrated novel pharmacological strategies to reverse this effect after the fact (Hymel et al., Behav Pharmacol, 25:599-608, 2014).

Screening of novel compounds as analgesics and therapeutics for drug abuse. This translational project has multiple components. First, we are screening peptide kappa opioid agonists and antagonists as therapeutics for cocaine abuse, examining compounds synthesized by the lab of Dr. Jane Aldrich. This work is ongoing, but we have already identified a systemically active peptide antagonist, zyklophin, that crosses the blood-brain barrier to suppress the stress-induced reinstatement of cocaine-conditioned place preference (Aldrich et al., Proc Natl. Acad Sci, USA, 106:18396-18401, 2009). In a recent extension of this research funded from NIH-NIDA (R01 DA018832-06 and R01 DA023924-06), we have identified a set of cyclic tetrapeptides which may have promise as both analgesics and therapeutics for drug abuse. The lead compounds in this series have demonstrated both mixed opioid-receptor agonism and kappa-opioid receptor antagonism (Ross et al., British Journal of Pharmacology, 165(4b):1097-1108, 2012), and after oral administration have proven effective in preventing both the acutely rewarding effects of cocaine and prevents both stress and drug-induced reinstatement of extinguished drug-seeking behavior (Aldrich et al., Journal of Natural Products, 76(3):433-438, 2013 and Eans et al., British Journal of Pharmacology, 169(2):426-436, 2013). New compounds arising from this series show greater efficacy in opioid activity while preventing relapse to extinguished cocaine-seeking behavior, and in recent tests, morphine-seeking behavior. These findings support the purpose of a recent project funded by the DoD (PR141230) to seek therapeutics for abuse of a broad range of psychostimulants.An additional collaboration seeking novel analgesics is currently underway with Dr. Chris McCurdy at the University of Mississippi. This collaboration has produced two lines of research. In the first, my lab is characterizing a novel sigma ligand for analgesic properties, recently finding that this lead compound relieves neuropathic pain without addictive properties or sedative effects. This work contributed justification for the first clinical trial in February, 2016 where a radiolabeled version of the lead compound was found to image the site of neuropathic injury. In a second project recently funded by NIDA (R01 DA034777), we are developing a series of small molecule guanidine-piperdines agonists and antagonists selective for neuropeptide FF (NPFF)-receptor subtypes. The lead compound in this project has been recently characterized as an NPFF-1 receptor antagonist (Journigan et al., Journal of Medicinal Chemistry, 57(21):8903-8927, 2014), and shown since to prevent acute morphine antinociceptive tolerance. In a continuation of this work, we are screening ligands with dual opioid- and NPFF-receptor activity. To date, we have identified a lead compound demonstrating mixed opioid agonism and NPFF-receptor antagonism which produce potent analgesia without tolerance.

Open Researcher and Contributor ID (ORCID)

0000-0001-9851-9342

Publications

2023
Solid-Phase Synthesis of the Bicyclic Peptide OL-CTOP Containing Two Disulfide Bridges, and an Assessment of Its In Vivo μ-Opioid Receptor Antagonism after Nasal Administration
Molecules. 28(4) [DOI] 10.3390/molecules28041822. [PMID] 36838810.
2023
Structure-based design of bitopic ligands for the µ-opioid receptor
Nature. 613(7945):767-774 [DOI] 10.1038/s41586-022-05588-y.
2022
An analog of [d-Trp]CJ-15,208 exhibits kappa opioid receptor antagonism following oral administration and prevents stress-induced reinstatement of extinguished morphine conditioned place preference.
Pharmacology, biochemistry, and behavior. 217 [DOI] 10.1016/j.pbb.2022.173405. [PMID] 35584724.
2022
Bis-Cyclic Guanidine Heterocyclic Peptidomimetics as Opioid Ligands with Mixed μ-, κ- and δ-Opioid Receptor Interactions: A Potential Approach to Novel Analgesics
International Journal of Molecular Sciences. 23(17) [DOI] 10.3390/ijms23179623. [PMID] 36077029.
2022
Characterization of CM-398, a Novel Selective Sigma-2 Receptor Ligand, as a Potential Therapeutic for Neuropathic Pain
Molecules. 27(11) [DOI] 10.3390/molecules27113617. [PMID] 35684553.
2022
Clathrin-nanoparticles deliver BDNF to hippocampus and enhance neurogenesis, synaptogenesis and cognition in HIV/neuroAIDS mouse model
Communications Biology. 5(1) [DOI] 10.1038/s42003-022-03177-3. [PMID] 35301411.
2022
Examination of the Novel Sigma-1 Receptor Antagonist, SI 1/28, for Antinociceptive and Anti-allodynic Efficacy against Multiple Types of Nociception with Fewer Liabilities of Use
International Journal of Molecular Sciences. 23(2) [DOI] 10.3390/ijms23020615. [PMID] 35054797.
2022
Expression of Human Immunodeficiency Virus Transactivator of Transcription (HIV-Tat1-86) Protein Alters Nociceptive Processing that is Sensitive to Anti-Oxidant and Anti-Inflammatory Interventions
Journal of Neuroimmune Pharmacology. 17(1-2):152-164 [DOI] 10.1007/s11481-021-09985-4. [PMID] 33619645.
2022
HIV-1 Tat and cocaine impact astrocytic energy reservoirs and epigenetic regulation by influencing the LINC01133-hsa-miR-4726-5p-NDUFA9 axis.
Molecular therapy. Nucleic acids. 29:243-258 [DOI] 10.1016/j.omtn.2022.07.001. [PMID] 35892093.
2022
Novel histone modifications in microglia derived from a mouse model of chronic pain.
Proteomics. 22(9) [DOI] 10.1002/pmic.202100137. [PMID] 35081661.
2022
Peptide Kappa Opioid Receptor Ligands and Their Potential for Drug Development.
Handbook of experimental pharmacology. 271:197-220 [DOI] 10.1007/164_2021_519. [PMID] 34463847.
2022
SRI-32743, a novel allosteric modulator, attenuates HIV-1 Tat protein-induced inhibition of the dopamine transporter and alleviates the potentiation of cocaine reward in HIV-1 Tat transgenic mice.
Neuropharmacology. 220 [DOI] 10.1016/j.neuropharm.2022.109239. [PMID] 36126727.
2021
A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects
Journal of Medicinal Chemistry. 64(18):13873-13892 [DOI] 10.1021/acs.jmedchem.1c01273. [PMID] 34505767.
2021
Binge ethanol consumption-associated behavioral impairments in male mice using a gelatin-based drinking-in-the dark model
Alcohol. 95:25-36 [DOI] 10.1016/j.alcohol.2021.05.001.
2021
Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site.
eLife. 10 [DOI] 10.7554/eLife.56519. [PMID] 33555255.
2021
Development of New Benzylpiperazine Derivatives as σ1 Receptor Ligands with in Vivo Antinociceptive and Anti-Allodynic Effects.
ACS chemical neuroscience. 12(11):2003-2012 [DOI] 10.1021/acschemneuro.1c00106. [PMID] 34019387.
2021
HIV-1 Tat and cocaine impact mitochondrial epigenetics: effects on DNA methylation
Epigenetics. 16(9):980-999 [DOI] 10.1080/15592294.2020.1834919. [PMID] 33100130.
2021
In vivo proton magnetic resonance spectroscopy detection of metabolite abnormalities in aged Tat-transgenic mouse brain.
GeroScience. [DOI] 10.1007/s11357-021-00354-w. [PMID] 33818687.
2021
Kratom Alkaloids as Probes for Opioid Receptor Function: Pharmacological Characterization of Minor Indole and Oxindole Alkaloids from Kratom.
ACS chemical neuroscience. 12(14):2661-2678 [DOI] 10.1021/acschemneuro.1c00149. [PMID] 34213886.
2021
Kratom Alkaloids, Natural and Semi-Synthetic, Show Less Physical Dependence and Ameliorate Opioid Withdrawal
Cellular and Molecular Neurobiology. 41(5):1131-1143 [DOI] 10.1007/s10571-020-01034-7. [PMID] 33433723.
2021
Mini review: Promotion of substance abuse in HIV patients: Biological mediation by HIV-1 Tat protein.
Neuroscience letters. 753 [DOI] 10.1016/j.neulet.2021.135877. [PMID] 33838257.
2021
Oxidative Metabolism as a Modulator of Kratom’s Biological Actions
Journal of Medicinal Chemistry. 64(22):16553-16572 [DOI] 10.1021/acs.jmedchem.1c01111. [PMID] 34783240.
2021
Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects.
Proceedings of the National Academy of Sciences of the United States of America. 118(16) [DOI] 10.1073/pnas.2000017118. [PMID] 33846240.
2020
[3H]Dopamine Uptake through the Dopamine and Norepinephrine Transporters is Decreased in the Prefrontal Cortex of Transgenic Mice Expressing HIV-1 Transactivator of Transcription Protein.
The Journal of pharmacology and experimental therapeutics. 374(2):241-251 [DOI] 10.1124/jpet.120.266023. [PMID] 32461322.
2020
Chronic Voluntary Binge Ethanol Consumption Causes Sex-Specific Differences in Microglial Signaling Pathways and Withdrawal-associated Behaviors in Mice.
Alcoholism, clinical and experimental research. 44(9):1791-1806 [DOI] 10.1111/acer.14420. [PMID] 32767774.
2020
Design, Synthesis, and Characterization of the Macrocyclic Tetrapeptide cyclo[Pro-Sar-Phe-d-Phe]: A Mixed Opioid Receptor Agonist-Antagonist Following Oral Administration.
ACS chemical neuroscience. 11(9):1324-1336 [DOI] 10.1021/acschemneuro.0c00086. [PMID] 32251585.
2020
Discovery of a Highly Selective Sigma-2 Receptor Ligand, 1-(4-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one (CM398), with Drug-Like Properties and Antinociceptive Effects In Vivo.
The AAPS journal. 22(5) [DOI] 10.1208/s12248-020-00472-x. [PMID] 32691179.
2020
HIV-Tat and Cocaine Impact Brain Energy Metabolism: Redox Modification and Mitochondrial Biogenesis Influence NRF Transcription-Mediated Neurodegeneration.
Molecular neurobiology. [DOI] 10.1007/s12035-020-02131-w. [PMID] 32978730.
2020
Lyophilized Kratom Tea as a Therapeutic Option for Opioid Dependence
Drug and Alcohol Dependence. 216 [DOI] 10.1016/j.drugalcdep.2020.108310.
2020
Multifunctional opioid receptor agonism and antagonism by a novel macrocyclic tetrapeptide prevents reinstatement of morphine‐seeking behaviour
British Journal of Pharmacology. 177(18):4209-4222 [DOI] 10.1111/bph.15165. [PMID] 32562259.
2020
Phenylalanine Stereoisomers of CJ-15,208 and [d-Trp]CJ-15,208 Exhibit Distinctly Different Opioid Activity Profiles
Molecules. 25(17) [DOI] 10.3390/molecules25173999. [PMID] 32887303.
2020
Preventing Morphine-Seeking Behavior through the Re-Engineering of Vincamine’s Biological Activity.
Journal of medicinal chemistry. 63(10):5119-5138 [DOI] 10.1021/acs.jmedchem.9b01924. [PMID] 31913038.
2020
Region-specific effects of HIV-1 Tat on intrinsic electrophysiological properties of pyramidal neurons in mouse prefrontal cortex and hippocampus
Journal of Neurophysiology. 123(4):1332-1341 [DOI] 10.1152/jn.00029.2020. [PMID] 32101482.
2019
Antinociceptive activity of thiazole-containing cyclized DAMGO and Leu-(Met) enkephalin analogs.
Organic & biomolecular chemistry. 17(21):5305-5315 [DOI] 10.1039/c9ob00882a. [PMID] 31094391.
2019
Characterization of Sigma 1 Receptor Antagonist CM-304 and Its Analog, AZ-66: Novel Therapeutics Against Allodynia and Induced Pain.
Frontiers in pharmacology. 10 [DOI] 10.3389/fphar.2019.00678. [PMID] 31258480.
2018
A stable isotope dilution tandem mass spectrometry method of major kavalactones and its applications.
PloS one. 13(5) [DOI] 10.1371/journal.pone.0197940. [PMID] 29795658.
2018
HIV-1 Tat regulation of dopamine transmission and microglial reactivity is brain region specific.
Glia. 66(9):1915-1928 [DOI] 10.1002/glia.23447. [PMID] 29733459.
2017
A one-pot multicomponent approach to a new series of morphine derivatives and their biological evaluation.
Organic & biomolecular chemistry. 15(37):7796-7801 [DOI] 10.1039/c7ob01924f. [PMID] 28875208.
2017
Conditional Human Immunodeficiency Virus Transactivator of Transcription Protein Expression Induces Depression-like Effects and Oxidative Stress.
Biological psychiatry. Cognitive neuroscience and neuroimaging. 2(7):599-609 [DOI] 10.1016/j.bpsc.2017.04.002. [PMID] 29057370.
2017
Selective κ receptor partial agonist HS666 produces potent antinociception without inducing aversion after i.c.v. administration in mice.
British journal of pharmacology. 174(15):2444-2456 [DOI] 10.1111/bph.13854. [PMID] 28494108.
2016
Altered Secondary Structure of Dynorphin a Associates With Loss of Opioid Signalling and Nmda-Mediated Excitotoxicity in Sca23
Human Molecular Genetics. 25(13):2728-2737 [DOI] 10.1093/hmg/ddw130.
2016
Direct Phenotypic Screening in Mice: Identification of Individual, Novel Antinociceptive Compounds from a Library of 734,821 Pyrrolidine Bis-piperazines.
ACS combinatorial science. 18(1):51-64 [DOI] 10.1021/acscombsci.5b00126. [PMID] 26651386.
2016
Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics With Mu Agonism and Delta Antagonism, Which Do Not Recruit Beta-Arrestin-2
Journal Of Medicinal Chemistry. 59(18):8381-8397 [DOI] 10.1021/acs.jmedchem.6b00748. [PMID] 27556704.
2015
Conditional Tat protein brain expression in the GT-tg bigenic mouse induces cerebral fractional anisotropy abnormalities.
Current HIV research. 13(1):3-9 [PMID] 25619988.
2015
Didehydro-cortistatin A inhibits HIV-1 Tat mediated neuroinflammation and prevents potentiation of cocaine reward in Tat transgenic mice.
Current HIV research. 13(1):64-79 [PMID] 25613133.
2015
Exposure to HIV-1 Tat in brain impairs sensorimotor gating and activates microglia in limbic and extralimbic brain regions of male mice.
Behavioural brain research. 291:209-218 [DOI] 10.1016/j.bbr.2015.05.021. [PMID] 26005128.
2015
Parallel Synthesis of Hexahydrodiimidazodiazepines Heterocyclic Peptidomimetics and Their in Vitro and in Vivo Activities at μ (MOR), δ (DOR), and κ (KOR) Opioid Receptors.
Journal of medicinal chemistry. 58(12):4905-17 [DOI] 10.1021/jm501637c. [PMID] 25996309.
2015
Synthesis and biological evaluations of novel endomorphin analogues containing α-hydroxy-β-phenylalanine (AHPBA) displaying mixed μ/δ opioid receptor agonist and δ opioid receptor antagonist activities.
European journal of medicinal chemistry. 92:270-81 [DOI] 10.1016/j.ejmech.2014.12.049. [PMID] 25559207.
2015
Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior.
ACS chemical neuroscience. 6(11):1813-24 [DOI] 10.1021/acschemneuro.5b00153. [PMID] 26325040.
2015
The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders.
Frontiers in microbiology. 6 [DOI] 10.3389/fmicb.2015.01164. [PMID] 26557111.
2014
Alanine analogues of [D-Trp]CJ-15,208: novel opioid activity profiles and prevention of drug- and stress-induced reinstatement of cocaine-seeking behaviour.
British journal of pharmacology. 171(13):3212-22 [DOI] 10.1111/bph.12664. [PMID] 24588614.
2014
Anxiety-like behavior of mice produced by conditional central expression of the HIV-1 regulatory protein, Tat.
Psychopharmacology. 231(11):2349-60 [DOI] 10.1007/s00213-013-3385-1. [PMID] 24352568.
2014
Effects of conditional central expression of HIV-1 tat protein to potentiate cocaine-mediated psychostimulation and reward among male mice.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 39(2):380-8 [DOI] 10.1038/npp.2013.201. [PMID] 23945478.
2014
Estrous cycle and HIV-1 Tat protein influence cocaine-conditioned place preference and induced locomotion of female mice.
Current HIV research. 12(6):388-96 [PMID] 25613137.
2014
HIV-1 Tat protein exposure potentiates ethanol reward and reinstates extinguished ethanol-conditioned place preference.
Current HIV research. 12(6):415-23 [PMID] 25760047.
2014
Nonpeptide small molecule agonist and antagonist original leads for neuropeptide FF1 and FF2 receptors.
Journal of medicinal chemistry. 57(21):8903-27 [DOI] 10.1021/jm500989n. [PMID] 25268943.
2014
Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS.
Hormones and behavior. 65(5):445-53 [DOI] 10.1016/j.yhbeh.2014.04.001. [PMID] 24726788.
2014
Stress-induced increases in depression-like and cocaine place-conditioned behaviors are reversed by disruption of memories during reconsolidation.
Behavioural pharmacology. 25(5-6):599-608 [DOI] 10.1097/FBP.0000000000000074. [PMID] 25083575.
2013
Central administration of angiotensin IV rapidly enhances novel object recognition among mice.
Neuropharmacology. 70:247-53 [DOI] 10.1016/j.neuropharm.2013.01.025. [PMID] 23416700.
2013
Conditional Tat protein expression in the GT-tg bigenic mouse brain induces gray matter density reductions.
Progress in neuro-psychopharmacology & biological psychiatry. 43:49-54 [DOI] 10.1016/j.pnpbp.2012.12.018. [PMID] 23269344.
2013
Discovery of novel antinociceptive α-conotoxin analogues from the direct in vivo screening of a synthetic mixture-based combinatorial library.
ACS combinatorial science. 15(3):153-61 [DOI] 10.1021/co300152x. [PMID] 23414173.
2013
Effects of the kappa opioid receptor antagonist, norbinaltorphimine, on stress and drug-induced reinstatement of nicotine-conditioned place preference in mice.
Psychopharmacology. 226(4):763-8 [DOI] 10.1007/s00213-012-2716-y. [PMID] 22526543.
2013
Inhibition of Gβγ-subunit signaling potentiates morphine-induced antinociception but not respiratory depression, constipation, locomotion, and reward.
Behavioural pharmacology. 24(2):144-52 [DOI] 10.1097/FBP.0b013e32835f3d2f. [PMID] 23412114.
2013
Physical presence of nor-binaltorphimine in mouse brain over 21 days after a single administration corresponds to its long-lasting antagonistic effect on κ-opioid receptors.
The Journal of pharmacology and experimental therapeutics. 346(3):545-54 [DOI] 10.1124/jpet.113.206086. [PMID] 23853171.
2013
The macrocyclic peptide natural product CJ-15,208 is orally active and prevents reinstatement of extinguished cocaine-seeking behavior.
Journal of natural products. 76(3):433-8 [DOI] 10.1021/np300697k. [PMID] 23327691.
2013
The macrocyclic tetrapeptide [D-Trp]CJ-15,208 produces short-acting κ opioid receptor antagonism in the CNS after oral administration.
British journal of pharmacology. 169(2):426-36 [DOI] 10.1111/bph.12132. [PMID] 23425081.
2012
Expression of HIV-Tat protein is associated with learning and memory deficits in the mouse.
Behavioural brain research. 229(1):48-56 [DOI] 10.1016/j.bbr.2011.12.019. [PMID] 22197678.
2012
Novel opioid cyclic tetrapeptides: Trp isomers of CJ-15,208 exhibit distinct opioid receptor agonism and short-acting κ opioid receptor antagonism.
British journal of pharmacology. 165(4b):1097-108 [DOI] 10.1111/j.1476-5381.2011.01544.x. [PMID] 21671905.
2012
Opioid Peptides: Potential for Drug Development.
Drug discovery today. Technologies. 9(1):e23-e31 [PMID] 23316256.
2012
Peptides derived from the prohormone proNPQ/spexin are potent central modulators of cardiovascular and renal function and nociception.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 26(2):947-54 [DOI] 10.1096/fj.11-192831. [PMID] 22038051.
2012
Targeting dynorphin/kappa opioid receptor systems to treat alcohol abuse and dependence.
Alcohol (Fayetteville, N.Y.). 46(4):359-70 [DOI] 10.1016/j.alcohol.2011.10.006. [PMID] 22459870.
2011
Kappa Opioid Receptor-Mediated Disruption of Novel Object Recognition: Relevance for Psychostimulant Treatment.
Journal of addiction research & therapy. S4 [PMID] 22900234.
2011
Pharmacological characterization of 2-methyl-N-((2′-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine (PF-04455242), a high-affinity antagonist selective for κ-opioid receptors.
The Journal of pharmacology and experimental therapeutics. 339(2):555-66 [DOI] 10.1124/jpet.111.185108. [PMID] 21821697.
2011
Unexpected opioid activity profiles of analogues of the novel peptide kappa opioid receptor ligand CJ-15,208.
ChemMedChem. 6(9):1739-45 [DOI] 10.1002/cmdc.201100113. [PMID] 21761566.
2010
Endogenous kappa-opioid mediation of stress-induced potentiation of ethanol-conditioned place preference and self-administration.
Psychopharmacology. 210(2):199-209 [DOI] 10.1007/s00213-010-1844-5. [PMID] 20401606.
2010
Identification of two novel, potent, low-liability antinociceptive compounds from the direct in vivo screening of a large mixture-based combinatorial library.
The AAPS journal. 12(3):318-29 [DOI] 10.1208/s12248-010-9191-3. [PMID] 20422341.
2010
Synthesis of CJ-15,208, a novel κ-opioid receptor antagonist.
Tetrahedron letters. 51(38):5020-5023 [PMID] 22865937.
2009
Endogenous kappa opioid activation mediates stress-induced deficits in learning and memory.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(13):4293-300 [DOI] 10.1523/JNEUROSCI.6146-08.2009. [PMID] 19339623.
2009
Northeast Under/graduate Research Organization for Neuroscience (NEURON): our 13th conference for neuroscience trainees and educators.
CBE life sciences education. 8(2):111-3 [DOI] 10.1187/cbe.08-08-0050. [PMID] 19487498.
2009
Northeast Under/graduate Research Organization for Neuroscience (NEURON): Our Thirteenth Conference for Neuroscience Trainees and Educators.
Journal of undergraduate neuroscience education : JUNE : a publication of FUN, Faculty for Undergraduate Neuroscience. 7(2):A65-8 [PMID] 23493230.
2009
Peptide kappa opioid receptor ligands: potential for drug development.
The AAPS journal. 11(2):312-22 [DOI] 10.1208/s12248-009-9105-4. [PMID] 19430912.
2009
Synthesis of cyclic tetrapeptide CJ 15,208: a novel kappa opioid receptor antagonist.
Advances in experimental medicine and biology. 611:269-70 [PMID] 19400188.
2009
Zyklophin, a systemically active selective kappa opioid receptor peptide antagonist with short duration of action.
Proceedings of the National Academy of Sciences of the United States of America. 106(43):18396-401 [DOI] 10.1073/pnas.0910180106. [PMID] 19841255.
2008
Antidepressant-like effects of the novel kappa opioid antagonist MCL-144B in the forced-swim test.
Pharmacology. 81(3):229-35 [DOI] 10.1159/000112867. [PMID] 18176093.
2007
Reinstatement of cocaine place-conditioning prevented by the peptide kappa-opioid receptor antagonist arodyn.
European journal of pharmacology. 569(1-2):84-9 [PMID] 17568579.
2006
Prior activation of kappa opioid receptors by U50,488 mimics repeated forced swim stress to potentiate cocaine place preference conditioning.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 31(4):787-94 [PMID] 16123754.
2006
Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 31(6):1241-8 [PMID] 16123746.
2004
Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 24(19):4576-84 [PMID] 15140929.
2004
Prolonged kappa opioid receptor phosphorylation mediated by G-protein receptor kinase underlies sustained analgesic tolerance.
The Journal of biological chemistry. 279(3):1810-8 [PMID] 14597630.
2003
Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 23(13):5674-83 [PMID] 12843270.
2003
Phosphorylation of a carboxyl-terminal serine within the kappa-opioid receptor produces desensitization and internalization.
The Journal of biological chemistry. 278(36):34631-40 [PMID] 12815037.
2002
8-Carboxamidocyclazocine: a long-acting, novel benzomorphan.
The Journal of pharmacology and experimental therapeutics. 302(1):374-80 [PMID] 12065740.
2001
Regulation of opioid receptor function by chronic agonist exposure: constitutive activity and desensitization.
Molecular pharmacology. 60(1):20-5 [PMID] 11408596.
2001
Tyrosine phosphorylation of the mu-opioid receptor regulates agonist intrinsic efficacy.
Molecular pharmacology. 59(6):1360-8 [PMID] 11353794.
2000
Partial opioids. Medications for the treatment of pain and drug abuse.
Annals of the New York Academy of Sciences. 909:1-11 [PMID] 10911920.
2000
Tyrosine phosphorylation of the kappa -opioid receptor regulates agonist efficacy.
The Journal of biological chemistry. 275(49):38281-5 [PMID] 10995763.
1999
Genetic alteration of phospholipase C beta3 expression modulates behavioral and cellular responses to mu opioids.
Proceedings of the National Academy of Sciences of the United States of America. 96(18):10385-90 [PMID] 10468617.
1999
Nitrocinnamoyl and chlorocinnamoyl derivatives of dihydrocodeinone: in vivo and in vitro characterization of mu-selective agonist and antagonist activity.
The Journal of pharmacology and experimental therapeutics. 289(1):304-11 [PMID] 10087018.
1997
14 beta-Chlorocinnamoylamino derivatives of metopon: long-term mu-opioid receptor antagonists.
European journal of pharmacology. 320(2-3):121-9 [PMID] 9059844.
1995
Metopon and two unique derivatives: affinity and selectivity for the multiple opioid receptors.
European journal of pharmacology. 294(1):201-6 [PMID] 8788432.
A novel mitragynine analog with low efficacy mu-opioid receptor agonism displays antinociception with attenuated adverse effects
. [DOI] 10.1101/2021.04.22.440994.
Peripheral kappa opioid receptor activation drives noxious cold hypersensitivity in mice
. [DOI] 10.1101/2020.10.04.325118.

Grants

Jan 2023 ACTIVE
In vivo characterization of bitopic cyclic ligands and analogs.
Role: Principal Investigator
Funding: UNIV OF HLTH SCIENCES & PHARM ST LOUIS
Nov 2022 – Jan 2023
Evaluation of novel compounds potentially targeting central sigma receptors using both in vivo and in vitro assays
Role: Co-Project Director/Principal Investigator
Funding: ALCHEM LABORATORIES, INC
Oct 2021 ACTIVE
Sparian Biosciences – McLaughlin
Role: Principal Investigator
Funding: SPARIAN BIOSCIENCES
Sep 2020 – Aug 2022
Pharmacological probes based on mitragynine pseudoindoxyl.
Role: Principal Investigator
Funding: UNIV OF HLTH SCIENCES & PHARM ST LOUIS via NATL INST OF HLTH NIDA
Sep 2020 – Aug 2021
Therapeutic and mechanistic evaluation of multifunctional opioids as improved treatments for pain and substance abuse
Role: Other
Funding: AMER FOU FOR PHARM EDU
Apr 2020 – Nov 2022
Synthesis and in vitro and in vivo screening of fused and tethered heterocyclic peptidomimetics for the discovery of new analgesics with decreased side effects
Role: Principal Investigator
Funding: FLORIDA INTERNATIONAL UNIV via NATL INST OF HLTH NIDA
Apr 2018 ACTIVE
Molecular mechanisms: Dysregulation of monoamine transporters by HIV-1 Tat and cocaine.
Role: Principal Investigator
Funding: UNIV OF SOUTH CAROLINA via NATL INST OF HLTH NIDA
Sep 2017 – Sep 2021
Sigma receptor ligands as non-opioid based pain management.
Role: Principal Investigator
Funding: US ARMY MED RES ACQUISITION
Apr 2017 – Aug 2019
Optimization of non-peptide probes for the NPFF receptor system
Role: Co-Investigator
Funding: NATL INST OF HLTH NIDA
Sep 2016 – Feb 2019
Novel Opioid Peptides for Nose to Brain Delivery
Role: Principal Investigator
Funding: FL ATLANTIC UNIV via NATL INST OF HLTH NIDA
Jun 2016 – May 2019
Knock-in mouse model of dopamine transporter-Tat Interaction underlying NeuroAIDS
Role: Principal Investigator
Funding: UNIV OF SOUTH CAROLINA via NATL INST OF HLTH NIDA
Sep 2015 – Aug 2019
Novel peptide antagonists as treatments for substance abuse
Role: Principal Investigator
Funding: US ARMY MED RES ACQUISITION
Sep 2015 – Aug 2017
Optimization of non-peptide probes for the NPFF Receptor system
Role: Principal Investigator
Funding: UNIVERSITY OF MISSISSIPPI via NATL INST OF HLTH NIDA
Aug 2015 – May 2022
HIV Tat protein mediation of neurochemical changes and increased opioid reward
Role: Principal Investigator
Funding: NATL INST OF HLTH NIDA
May 2015 – Oct 2017
Tat mediation of HIV-associated mood disorders via
Role: Principal Investigator
Funding: NATL INST OF HLTH NIMH
Apr 2015 – Mar 2021
Peptidic Kappa Opioid Receptor Ligands as Potential Treatments for Drug Addiction
Role: Project Manager
Funding: NATL INST OF HLTH NIDA
Mar 2015 – Feb 2018
Peptidic Ligands for Kappa Opioid Receptors
Role: Project Manager
Funding: NATL INST OF HLTH NIDA

Education

Ph.D. – Neuroscience
1998 · University of Rochester
M. S. – Neuroscience
1996 · University of Rochester
B.A. – Biology
1989 · University of California at Santa Cruz

Contact Details

Phones:
Business:
(352) 273-7207
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