nitroglycerin (nitroglycerin, I2R / NitroMist)

Photobiomodulation and Migraine: Mechanisms and Therapeutic Potential.

Machado Lucas da Silva LDS, Schwartz Allan Yukawa AY, Lizarelli Rosane de Fátima Zanirato RFZ, Salgado Afonso Shiguemi Inoue ASI et al.

Background: Migraine is a prevalent and disabling neurological disorder involving mitochondrial dysfunction, neuroinflammation, altered cortical excitability, and neurovascular dysregulation. Photobiomodulation, a noninvasive intervention based on red or near-infrared light, has emerged as a promising strategy due to its multimodal biological effects.Objective: This narrative review aimed to synthesize current evidence on the biological mechanisms and therapeutic potential of photobiomodulation in migraine.Methods: A literature search was conducted in PubMed/MEDLINE for studies published up to June 2026, focusing on photobiomodulation, low-level laser therapy, migraine, headache, and related biological mechanisms.Results: Mechanistic evidence indicates that photobiomodulation enhances mitochondrial respiration, increases ATP production, restores redox homeostasis, and modulates nitric oxide signaling, contributing to improved cerebral perfusion and neurovascular coupling. In addition, photobiomodulation attenuates neuroinflammatory responses by reducing pro-inflammatory cytokines and glial activation while promoting neuroplasticity and cortical homeostasis. Preclinical models relevant to migraine, including trigeminovascular activation, nitroglycerin-induced hypersensitivity, and cortical spreading depression, support its translational plausibility by demonstrating reductions in hyperalgesia, oxidative stress, and neural inflammation.Conclusion: Although migraine-specific evidence remains limited, photobiomodulation represents a safe and potentially disease-modifying therapeutic approach. Future controlled clinical trials are needed to determine optimal stimulation parameters and clinical efficacy in migraine management.

Nitroglycerin and Chest Pain for the Anesthesia Team: Optimizing Pulse Field Ablations.

Khoche Swapnil S, Roberson Jesse J, Cronin Brett B

Peculiar stimulatory action of high-energy chemicals: Fifty years of explosive-induced hormesis evidence.

Agathokleous Evgenios E, Sun Xingyue X, Carvalho Marcia E A MEA, Liu Haitao H et al.

Explosives, such as trinitrotoluene (TNT) and cyclic nitramines (cyclotrimethylene trinitramine, RDX, and cyclotetramethylene tetranitramine, HMX), are widespread environmental contaminants. Although high doses are toxic, the effects of low, environmentally relevant concentrations remain poorly characterized in risk assessment. This review synthesizes evidence from five decades of research to determine explosives-induced hormesis, a biphasic dose-response characterized by stimulation at low doses and inhibition at high doses. Hormetic responses to explosives have been documented across a vast range of life forms, including bacteria, algae, higher plants, annelid worms, crustaceans, insects, fish, reptiles, and mammalian cells. Stimulated endpoints include growth, reproduction, chlorophyll content, reduced DNA damage, and stem cell proliferation. Effective concentrations span seven orders of magnitude, from 0.0014 mg kg-1 to 21,750 mg kg-1. Key explosive classes inducing hormesis include nitroaromatics (TNT, 1,3,5-trinitrobenzene, TNB, picric acid), nitramines (RDX, HMX), and nitrate esters (nitroglycerin). These findings challenge traditional linear or threshold dose-response models used in ecological risk assessment, and highlight the need to revise standard testing protocols to include low-concentration treatments and hormesis modeling.

Structure-Function Analysis of the Benzyloxy Moiety of the Delta-Opioid Receptor Positive Modulator BMS-986187: Identification of a Derivative with High Selectivity for the Delta-Opioid Receptor over the Mu-Opioid Receptor In Vitro and In Vivo.

Li Mengchu M, Zhang Sherrice S, Powell Alexander J AJ, Stewart Hannah C HC et al.

Positive allosteric modulators (PAMs) of the delta-opioid receptor (DOR) enhance endogenous opioid signaling while avoiding the convulsant liability of orthosteric agonists. However, the prototypical DOR-PAM, BMS-986187, also potentiates mu-opioid receptor (MOR) signaling, raising concerns regarding respiratory depression and abuse liability. Here, we report a structure-activity study of the benzyloxy moiety of BMS-986187 to improve selectivity for DOR over MOR, while retaining DOR-PAM potency. Fifty-two new analogues and 12 previously reported ones featuring mono- and disubstitution of the benzyl ring and phenyl-heterocycle replacements were synthesized and evaluated in β-arrestin2 recruitment assays. Ortho-substituted derivatives consistently enhanced DOR-PAM potency, although often increased MOR-PAM activity. One pyridyl derivative (compound 35) retained high DOR-PAM potency and efficacy (EC50 = 0.1 μM, Emax = 91%) with no detectable MOR activity. In mice, compound 35 enhanced DOR-mediated reversal of nitroglycerin-induced hyperalgesia, an effect absent in DOR-knockout mice, without enhancing MOR-mediated antinociception, demonstrating in vivo selectivity.