IBNtxA (3'-iodobenzoyl-6β-naltrexamide) is a potent analgesic in mice lacking many traditional opioid side effects. In mice, it displays no respiratory depression, does not produce physical dependence with chronic administration, and shows no cross-tolerance to morphine. It has limited effects on gastrointestinal transit and shows no reward behavior. Biochemical studies indicate its actions are mediated through a set of μ-opioid receptor clone MOR-1 splice variants associated with exon 11 that lack exon 1 and contain only six transmembrane domains. Like the mouse and human, rats express exon 11-associated splice variants that also contain only six transmembrane domains, raising the question of whether IBNtxA would have a similar pharmacologic profile in rats. When given systemically, IBNtxA is a potent analgesic in rats, with an ED50 value of 0.89 mg/kg s.c., approximately 4-fold more potent than morphine. It shows no analgesic cross-tolerance in morphine-pelleted rats. IBNtxA displays no respiratory depression as measured by blood oxygen saturation. In contrast, oximetry shows that an equianalgesic dose of morphine lowers blood oxygen saturation values by 30%. IBNtxA binding is present in a number of brain regions, with the thalamus standing out with very high levels and the cerebellum with low levels. As in mice, IBNtxA is a potent analgesic in rats with a favorable pharmacologic profile and reduced side effects.
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http://dx.doi.org/10.1124/jpet.114.213199 | DOI Listing |
Physiol Behav
January 2025
Department of Nursing, Nantong First People's Hospital, Nantong, Jiangsu, 226001, China. Electronic address:
Haemorrhoids are a common anorectal disease primarily treated through surgery, often leading to complications such as pain. The efficacy of acupuncture in relieving postoperative pain in mixed haemorrhoids has not been well-documented. This study included 90 patients undergoing haemorrhoid surgery and their Visual Analogue Score (VAS), inflammatory factor levels, Hamilton Depression Rating Scale (HAMD), and analgesic drug use were accessed.
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Department of Obstetrics and Gynecology, University of Florence, Careggi University Hospital, Florence, Italy.
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View Article and Find Full Text PDFSci Rep
January 2025
Gubra ApS, Hørsholm Kongevej 11B, DK-2970, Hørsholm, Denmark.
Migraine is a debilitating headache disorder. The disease has neurovascular origin and migraine attacks can be elicited by vasodilative neuropeptides such as alpha calcitonin gene-related peptide (αCGRP). Antagonizing CGRP actions in migraine patients has proven clinically efficient.
View Article and Find Full Text PDFInt J Pharm
January 2025
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, PR China. Electronic address:
Ketorolac, a nonsteroidal anti-inflammatory drug, exhibits moderate antipyretic and anti-inflammatory properties, as well as potent analgesic effects. It is widely used in clinical practice for pain relief in cases of mild and severe pain such as postoperative pain, fractures, sprains, toothaches and cancer pain. Due to its relatively short half-life, patients experiencing pain often need frequent injections or oral medications, leading to poor patient compliance.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405.
Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects.
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