Jay P. McLaughlin
YOU?
Author Swipe
View article: Structure-guided design of partial agonists at an opioid receptor
Structure-guided design of partial agonists at an opioid receptor Open
Chronic pain and opioid overdose deaths highlight the need for non-addictive analgesics with novel mechanisms. The δ opioid receptor (δOR) is a promising target, as it lacks the respiratory depression associated with µ opioid receptor (µOR…
View article: Total synthesis and biological activity of "carbamorphine": O-to-CH2 replacement in the E-ring of the morphine core structure.
Total synthesis and biological activity of "carbamorphine": O-to-CH2 replacement in the E-ring of the morphine core structure. Open
Morphine is a µ-opioid receptor (MOR) agonist and potent analgesic. However, it displays several side effects including respiratory depression and addiction. Here, we show that a single heavy atom replacement in the morphine core structure…
View article: Optimization of the Macrocyclic Tetrapeptide [D-Trp]CJ-15,208 to Prevent Stress-Induced Relapse of Cocaine-Seeking Behavior
Optimization of the Macrocyclic Tetrapeptide [D-Trp]CJ-15,208 to Prevent Stress-Induced Relapse of Cocaine-Seeking Behavior Open
Kappa opioid receptor (KOR) antagonists may have therapeutic potential to prevent stress-induced relapse in abstinent individuals with cocaine use disorder (CUD). The macrocyclic peptide [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) is an …
View article: Dual Opioid–Neuropeptide FF Small Molecule Ligands Demonstrate Analgesia with Reduced Tolerance Liabilities
Dual Opioid–Neuropeptide FF Small Molecule Ligands Demonstrate Analgesia with Reduced Tolerance Liabilities Open
Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds syn…
View article: Total synthesis and biological activity of “carbamorphine”: O-to-CH <sub>2</sub> replacement in the E-ring of the morphine core structure
Total synthesis and biological activity of “carbamorphine”: O-to-CH <sub>2</sub> replacement in the E-ring of the morphine core structure Open
Morphine is a µ-opioid receptor (MOR) agonist and potent analgesic. However, it displays several side effects including respiratory depression and addiction. Here, we show that a single heavy atom replacement in the morphine core structure…
View article: Epigenetics and Mitochondrial Biogenesis: The Role of Sirtuins in HIV Neuropathogenesis
Epigenetics and Mitochondrial Biogenesis: The Role of Sirtuins in HIV Neuropathogenesis Open
Mitochondrial energy deficits play a central role in HIV-associated neurocognitive disorder (HAND). HIV disrupts cellular functions, including epigenetic modifications such as class III histone deacetylation mediated by sirtuins (SIRTs). H…
View article: PRX-3140, a 5-HT4 Partial Agonist and Sigma-1 Agonist/Antagonist, Modulates Glucocorticoid Insulin Suppression and Cortisol Levels
PRX-3140, a 5-HT4 Partial Agonist and Sigma-1 Agonist/Antagonist, Modulates Glucocorticoid Insulin Suppression and Cortisol Levels Open
PRX-3140 is a partial agonist to the 5-hydroxytryptamine receptor 4 (5-HT4) and a ligand for the sigma-1 (S1R) and sigma-2 (S2R) receptors. Although few publications have inferred S1R agonists/antagonists modulate blood glucose, Di et.al (…
View article: Conformational Plasticity Enhances the Brain Penetration of a Metabolically Stable, Dual-Functional Opioid-Peptide CycloAnt
Conformational Plasticity Enhances the Brain Penetration of a Metabolically Stable, Dual-Functional Opioid-Peptide CycloAnt Open
CycloAnt is an opioid peptide that produces potent and efficacious antinociception with significantly reduced side effects upon systemic administration in mice. To verify its CNS-mediated antinociception, we determined its binding affinity…
View article: Signaling Modulation Mediated by Ligand Water Interactions with the Sodium Site at μOR
Signaling Modulation Mediated by Ligand Water Interactions with the Sodium Site at μOR Open
The mu opioid receptor (μOR) is a target for clinically used analgesics. However, adverse effects, such as respiratory depression and physical dependence, necessitate the development of alternative treatments. Recently we reported a novel …
View article: Structure-Guided Design of Partial Agonists at an Opioid Receptor
Structure-Guided Design of Partial Agonists at an Opioid Receptor Open
The persistence of chronic pain and continuing overdose deaths from pain-relieving opioids targeting µ opioid receptor (µOR) have fueled the need for reliable long-term analgesics which use different targets and mechanisms. The δ opioid re…
View article: Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS
Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS Open
Although treatable with antiretroviral therapy, HIV infection persists in people living with HIV (PLWH). It is well known that the HIV virus finds refuge in places for which antiretroviral medications do not reach therapeutic levels, mainl…
View article: SRI-30827, a novel allosteric modulator of the dopamine transporter, alleviates HIV-1 Tat-induced potentiation of cocaine conditioned place preference in mice
SRI-30827, a novel allosteric modulator of the dopamine transporter, alleviates HIV-1 Tat-induced potentiation of cocaine conditioned place preference in mice Open
Objectives HIV-1 Tat (transactivator of transcription) protein disrupts dopaminergic transmission and potentiates the rewarding effects of cocaine. Allosteric modulators of the dopamine transporter (DAT) have been shown to reverse Tat-indu…
View article: Identification and Pharmacological Characterization of a Low-Liability Antinociceptive Bifunctional MOR/DOR Cyclic Peptide
Identification and Pharmacological Characterization of a Low-Liability Antinociceptive Bifunctional MOR/DOR Cyclic Peptide Open
Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library c…
View article: Identification and Pharmacological Characterization of A Low-Liability Antinociceptive Bifunctional MOR/DOR Cyclic Peptide
Identification and Pharmacological Characterization of A Low-Liability Antinociceptive Bifunctional MOR/DOR Cyclic Peptide Open
Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library c…
View article: Negative allosteric modulation of the µ-opioid receptor
Negative allosteric modulation of the µ-opioid receptor Open
The µ-opioid receptor (µOR) is a well-established target for analgesia, yet conventional opioid receptor agonists cause serious adverse effects, notably addiction and respiratory depression, which have led to the present opioid overdose ep…
View article: Tryptophan Substitution in CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]) Introduces δ-Opioid Receptor Antagonism, Preventing Antinociceptive Tolerance and Stress-Induced Reinstatement of Extinguished Cocaine-Conditioned Place Preference
Tryptophan Substitution in CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]) Introduces δ-Opioid Receptor Antagonism, Preventing Antinociceptive Tolerance and Stress-Induced Reinstatement of Extinguished Cocaine-Conditioned Place Preference Open
The macrocyclic tetrapeptide CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]) and its D-Trp isomer exhibit kappa opioid receptor (KOR) antagonism which prevents stress-induced reinstatement of extinguished cocaine-conditioned place preference. Here, w…
View article: Circadian disruption and psychostimulants dysregulates plasma acute-phase proteins and circulating cell-free mitochondrial DNA
Circadian disruption and psychostimulants dysregulates plasma acute-phase proteins and circulating cell-free mitochondrial DNA Open
The findings of our study affirm that the levels of CRP, C3, SAA, and cortisol, which reflect inflammation, are enhanced by circadian disruption, cocaine, and METH, and these levels show a strong correlation with the content of circulating…
View article: 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
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 Open
New strategies facilitate the design of cyclic peptides which can penetrate the brain. We have designed a bicyclic peptide, OL-CTOP, composed of the sequences of a selective μ-opioid receptor antagonist, CTOP (f-cyclo(CYwOTX)T) (X = penici…
View article: Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures
Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures Open
Disturbances in the circadian rhythm alter the normal sleep-wake cycle, which increases vulnerability to drug abuse. Drug abuse can disrupt several homeostatic processes regulated by the circadian rhythm and influence addiction paradigms, …
View article: Bis-Cyclic Guanidine Heterocyclic Peptidomimetics as Opioid Ligands with Mixed μ-, κ- and δ-Opioid Receptor Interactions: A Potential Approach to Novel Analgesics
Bis-Cyclic Guanidine Heterocyclic Peptidomimetics as Opioid Ligands with Mixed μ-, κ- and δ-Opioid Receptor Interactions: A Potential Approach to Novel Analgesics Open
The design and development of analgesics with mixed-opioid receptor interactions has been reported to decrease side effects, minimizing respiratory depression and reinforcing properties to generate safer analgesic therapeutics. We synthesi…
View article: Characterization of CM-398, a Novel Selective Sigma-2 Receptor Ligand, as a Potential Therapeutic for Neuropathic Pain
Characterization of CM-398, a Novel Selective Sigma-2 Receptor Ligand, as a Potential Therapeutic for Neuropathic Pain Open
Sigma receptors modulate nociception, offering a potential therapeutic target to treat pain, but relatively little is known regarding the role of sigma-2 receptors (S2R) in nociception. The purpose of this study was to investigate the in v…