Kirk W. Johnson
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View article: Mechanisms of bacterial heme uptake and degradation: Diverse strategies for ring opening
Mechanisms of bacterial heme uptake and degradation: Diverse strategies for ring opening Open
Iron acquisition by bacterial pathogens is critical for their survival and virulence within the host. Heme represents a viable source of iron by which pathogens overcome the limited iron availability and establish infection. Over the past …
View article: Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine
Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine Open
Aim LY3451838 is a monoclonal antibody against pituitary adenylate cyclase-activating peptide (PACAP), a target in migraine research. The present study aimed to evaluate LY3451838 as a preventive treatment for participants with treatment-r…
View article: Galcanezumab reduces trigeminal nociception and is effective in preclinical models of migraine and trigeminal autonomic cephalalgias
Galcanezumab reduces trigeminal nociception and is effective in preclinical models of migraine and trigeminal autonomic cephalalgias Open
Objectives/Background This study was undertaken to assess the therapeutic efficacy of galcanezumab in preclinical models of migraine and cluster headache and to determine potential shared trigeminovascular mechanisms of action. Galcanezuma…
View article: Preclinical and clinical evaluation of a novel TRPA1 antagonist LY3526318
Preclinical and clinical evaluation of a novel TRPA1 antagonist LY3526318 Open
The transient receptor potential cation channel member A1 (TRPA1) is heavily implicated in nociceptive signaling in both physiological and pathological pain states. However, it has been challenging to develop TRPA1 antagonists with appropr…
View article: Application of preclinical absorption, distribution, metabolism, elimination in vitro techniques for the characterization and compound library optimization of novel antibiotic gallium salophen
Application of preclinical absorption, distribution, metabolism, elimination in vitro techniques for the characterization and compound library optimization of novel antibiotic gallium salophen Open
View article: Clinical proof-of-concept results with a novel TRPA1 antagonist (LY3526318) in 3 chronic pain states
Clinical proof-of-concept results with a novel TRPA1 antagonist (LY3526318) in 3 chronic pain states Open
Transient receptor potential ankyrin 1 (TRPA1) is implicated in physiological and pathological nociceptive signaling, but the clinical benefit of TRPA1 antagonists in chronic pain is not clearly demonstrated. LY3526318 is an oral, potent, …
View article: Distinctive Neurophysiological Signatures of Analgesia after Inflammatory Pain in the ACC of Freely Moving Mice
Distinctive Neurophysiological Signatures of Analgesia after Inflammatory Pain in the ACC of Freely Moving Mice Open
Preclinical assessments of pain have often relied upon behavioral measurements and anesthetized neurophysiological recordings. Current technologies enabling large-scale neural recordings, however, have the potential to unveil quantifiable …
View article: TRPA1 Antagonist LY3526318 Inhibits the Cinnamaldehyde‐Evoked Dermal Blood Flow Increase: Translational Proof of Pharmacology
TRPA1 Antagonist LY3526318 Inhibits the Cinnamaldehyde‐Evoked Dermal Blood Flow Increase: Translational Proof of Pharmacology Open
Transient receptor potential Ankyrin 1 (TRPA1) is an ion channel expressed by sensory neurons, where it mediates pain signaling. Consequently, it has emerged as a promising target for novel analgesics, yet, to date, no TRPA1 antagonists ha…
View article: Evaluation of Plasma Calcitonin Gene-Related Peptide as a Biomarker for Painful Temporomandibular Disorder and Migraine
Evaluation of Plasma Calcitonin Gene-Related Peptide as a Biomarker for Painful Temporomandibular Disorder and Migraine Open
In this well-powered study, interictal plasma concentration of CGRP was a poor biomarker for TMD and migraine.
View article: Airway soluble CSF1R predicts progression in patients with idiopathic pulmonary fibrosis
Airway soluble CSF1R predicts progression in patients with idiopathic pulmonary fibrosis Open
This study provides the first evidence for a role of airway sCSF1R in IPF https://bit.ly/3KTBrCA.
View article: Characterization of transit rates in the large intestine of mice following treatment with a <scp>CGRP</scp> antibody, <scp>CGRP</scp> receptor antibody, and small molecule <scp>CGRP</scp> receptor antagonists
Characterization of transit rates in the large intestine of mice following treatment with a <span>CGRP</span> antibody, <span>CGRP</span> receptor antibody, and small molecule <span>CGRP</span> receptor antagonists Open
Objective To characterize the effects of blocking calcitonin gene‐related peptide (CGRP) activity in a mouse model of gastrointestinal transport. Background Migraine management using CGRP modulating therapies can cause constipation of vary…
View article: The selective 5‐HT<sub>1F</sub> receptor agonist lasmiditan inhibits trigeminal nociceptive processing: Implications for migraine and cluster headache
The selective 5‐HT<sub>1F</sub> receptor agonist lasmiditan inhibits trigeminal nociceptive processing: Implications for migraine and cluster headache Open
Background and Purpose Lasmiditan is a novel selective 5‐HT 1F receptor agonist, recently approved for acute treatment of migraine. 5‐HT 1F receptors are widely expressed in the CNS and trigeminovascular system. Here, we have explored the …
View article: Levels of prolactin and testosterone and associated sexual dysfunction and breast abnormalities in men with schizophrenia treated with antipsychotic medications
Levels of prolactin and testosterone and associated sexual dysfunction and breast abnormalities in men with schizophrenia treated with antipsychotic medications Open
Sexual dysfunction is one of the most bothersome adverse drug effects seen in men and women taking antipsychotic medications and negatively impacts medication adherence. Antipsychotic medications are associated with hyperprolactinemia, whi…
View article: A Single and Repeat-Dose Study of RZ358 in Patients With Post-Gastric Bypass Hypoglycemia (PGBH): Results of Population Pharmacokinetic (PK) / Pharmacodynamic (PD) Modeling
A Single and Repeat-Dose Study of RZ358 in Patients With Post-Gastric Bypass Hypoglycemia (PGBH): Results of Population Pharmacokinetic (PK) / Pharmacodynamic (PD) Modeling Open
PGBH is an uncommon individual risk but nevertheless cumulatively prevalent and important consequence of gastric bypass for the management of obesity. It is characterized by dysregulated hyperinsulinism (HI) and significant postprandial hy…
View article: Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache
Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache Open
Background Medication overuse is a significant issue that complicates the treatment of headache disorders. The most effective medications for the acute treatment of migraine all have the capacity to induce medication overuse headache (MOH)…
View article: Lasmiditan mechanism of action – review of a selective 5-HT1F agonist
Lasmiditan mechanism of action – review of a selective 5-HT1F agonist Open
View article: Lasmiditan inhibits calcitonin gene-related peptide release in the rodent trigeminovascular system
Lasmiditan inhibits calcitonin gene-related peptide release in the rodent trigeminovascular system Open
Migraine headache pathophysiology involves trigeminovascular system activation, calcitonin gene-related peptide (CGRP) release, and dysfunctional nociceptive transmission. Triptans are 5-HT 1B/1D/(1F) receptor agonists that prejunctionally…
View article: Characterization of binding, functional activity, and contractile responses of the selective 5‐HT<sub>1F</sub> receptor agonist lasmiditan
Characterization of binding, functional activity, and contractile responses of the selective 5‐HT<sub>1F</sub> receptor agonist lasmiditan Open
Background and Purpose Triptans are 5‐HT 1B/1D receptor agonists (that also display 5‐HT 1F receptor affinity) with antimigraine action, contraindicated in patients with coronary artery disease due to their vasoconstrictor properties. Conv…
View article: Issue Information
Issue Information Open
View article: CGRP and the Trigeminal System in Migraine
CGRP and the Trigeminal System in Migraine Open
Objective The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene‐related peptide (CGRP) within the context of the trigeminovascular system. Background Migrai…
View article: A unique allosteric insulin receptor monoclonal antibody that prevents hypoglycemia in the SUR-1<sup>−/−</sup> mouse model of KATP hyperinsulinism
A unique allosteric insulin receptor monoclonal antibody that prevents hypoglycemia in the SUR-1<sup>−/−</sup> mouse model of KATP hyperinsulinism Open
Loss-of-function mutations of the ß-cell ATP-sensitive potassium channels (KATP) cause the most common and severe form of congenital hyperinsulinism (KATPHI), a disorder of ß-cell function characterized by severe hypo…
View article: Effect of Different Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention
Effect of Different Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention Open
clinicaltrials.gov Identifier: NCT02163993.
View article: Synthesis, Binding Mode, and Antihyperglycemic Activity of Potent and Selective (5-Imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine Inhibitors of Glycogen Synthase Kinase 3
Synthesis, Binding Mode, and Antihyperglycemic Activity of Potent and Selective (5-Imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine Inhibitors of Glycogen Synthase Kinase 3 Open
In an effort to identify new antidiabetic agents, we have discovered a novel family of (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine analogues which are inhibitors of human glycogen synthase kinase 3 (GSK3). We dev…
View article: Attenuation of Insulin Action by an Allosteric Insulin Receptor Antibody in Healthy Volunteers
Attenuation of Insulin Action by an Allosteric Insulin Receptor Antibody in Healthy Volunteers Open
Single X358 infusions were well tolerated and resulted in a dose-dependent reduction in insulin sensitivity. Clinical development of X358 in hyperinsulinemic, hypoglycemic conditions is proceeding.
View article: Effects of Ibudilast on the Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Recently Detoxified Adults with Opioid Dependence
Effects of Ibudilast on the Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Recently Detoxified Adults with Opioid Dependence Open
View article: CGRP receptor activity in mice with global expression of human receptor activity modifying protein 1
CGRP receptor activity in mice with global expression of human receptor activity modifying protein 1 Open
Background and Purpose CGRP is a potent vasodilator and nociceptive neuropeptide linked to migraine. CGRP receptors are heterodimers of receptor activity modifying protein 1 (RAMP1) and either calcitonin receptor‐like receptor (CLR; forms …
View article: Supradural inflammatory soup in awake and freely moving rats induces facial allodynia that is blocked by putative immune modulators
Supradural inflammatory soup in awake and freely moving rats induces facial allodynia that is blocked by putative immune modulators Open
View article: The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine
The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine Open
Calcitonin gene–related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene–related peptide wa…
View article: Monoclonal antibodies for chronic pain: A practical review of mechanisms and clinical applications
Monoclonal antibodies for chronic pain: A practical review of mechanisms and clinical applications Open
Context Monoclonal antibodies are being investigated for chronic pain to overcome the shortcomings of current treatment options. Objective To provide a practical overview of monoclonal antibodies in clinical development for use in chronic …
View article: Discovery of dual positive allosteric modulators (PAMs) of the metabotropic glutamate 2 receptor and CysLT1 antagonists for treating migraine headache
Discovery of dual positive allosteric modulators (PAMs) of the metabotropic glutamate 2 receptor and CysLT1 antagonists for treating migraine headache Open