tebanicline (ABT-594) / AbbVie - LARVOL DELTA

Molecular insights into the α6β4 nicotinic acetylcholine receptor function and ligand recognition. (PubMed, Nat Commun) - "Furthermore, we identify the binding pockets for nicotine and tebanicline, demonstrating the essential residues contributing to ligand affinity and providing detailed molecular insights into why these agonists have different binding affinities despite both occupying the orthosteric site of the α6β4 receptor. These structures offer significant molecular insight into the function and ligand recognition of α6β4 receptor."

Journal • Pain

INHIBITION OF ΑLPHA-4 ΒETA-2 NICOTINIC ACETYLCHOLINE RECEPTOR ATTENUATES SYSTEMIC INFLAMMATION AND NEUROINFLAMMATION TRIGGERED BY LAPAROTOMY (ADPD 2023) - " C57BL/6J mice were employed with the administrat ion of α4β2 -nAChR partial agonists for three days, and they were subjected to laparotomy or anesthesia group (2.5 % sevoflurane, 800 ml/min oxygen)... Pro-inflammatory cytokines increased significantly in liver and hippocampus 4 hours after laparotomy, while the administration of agonist of α4β2nAChR, ABT594 reduced the levels of some pro -inflammatory cytokines... Taken together, specific knock -out of α4 -nAChR in mice can attenuate the surgery induced systemic inflammation and neuroinflammation. These data suggest that cholinergic anti -inflammatory pathway have an anti - inflammatory effect in laparotomy model. The study is supporte d by General Research Fund from Research Grant Council GRF17120119."

Anesthesia • CNS Disorders • Cognitive Disorders • Immunology • Inflammation

Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons. (PubMed, Arch Toxicol) - "The pesticides (at 3-30 µM) also blunted the response to the non-α7 agonist ABT 594 in LUHMES cells. These data show that human neuronal cells are functionally affected by low micromolar concentrations of several neonicotinoids. An effect of such signals on nervous system development is a toxicological concern."

Journal • Neuroblastoma • Oncology • Solid Tumor

Countering Opioid-induced Respiratory Depression in Male Rats with Nicotinic Acetylcholine Receptor Partial Agonists Varenicline and ABT 594. (PubMed, Anesthesiology) - "Activation of α4β2 nicotinic acetylcholine receptors by varenicline and ABT 594 counters opioid-induced respiratory depression without interfering with analgesia."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Mood Disorders • Pain • Tobacco Cessation

Optical probing of acetylcholine receptors on neurons in the medial habenula with a novel caged nicotine drug analogue. (PubMed, J Physiol) - "We developed a new caged nicotinic acetylcholine receptor (nAChR) agonist, ABT594, which is photolyzed by one- and two-photon excitation. The caged compound is photolyzed with a quantum yield of 0.20 One-photon uncaging of ABT594 elicited large currents and Ca transients at the soma and dendrites of medial habenula (MHb) neurons of mouse brain slices. Unexpectedly, uncaging of ABT594 also revealed highly Ca -permeable nAChRs on axons of MHb neurons."

Journal

Epibatidine: A Promising Natural Alkaloid in Health. (PubMed, Biomolecules) - "On the other hand, many reports are devoted to structure⁻activity relationships to obtain optically active epibatidine and its analogues, and to access its pharmacological effects. Although pharmacological results are obtained from experimental studies and only a few clinical trials, new perspectives are open for the discovery of new drug therapies."

Journal • Review