The effects of chronically administered corticosterone on the responses of the rat isolated anococcygeus muscle to agonists (acetylcholine, norepinephrine) were compared with those of morphine withdrawal in intact or metyrapone-pretreated rats and with those of a single dose of reserpine in intact or adrenalectomized rats. The possibility that the similar supersensitivity, which occurs in thyroidectomized rats, might be associated with elevated corticosterone levels was investigated by measuring fluorimetrically the plasma levels of corticosterone in thyroidectomized rats. Corticosterone, morphine withdrawal or a single dose of reserpine produced similar supersensitivities, characterized by increased maximum responses to both agonists (acetylcholine, norepinephrine) and an increased pD2 value for acetylcholine. This effect of morphine withdrawal together with the weight loss characteristic of this condition was absent in metyrapone-pretreated rats. A single dose of reserpine had no effect in adrenalectomized rats. Plasma corticosterone levels were elevated in thyroidectomized rats. These results suggest that the common factor underlying the identical supersensitivities produced by corticosterone, morphine withdrawal, a single dose of reserpine or thyroidectomy is the ability of each treatment to raise plasma corticosterone levels.
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Large library docking of tangible molecules has revealed potent ligands across many targets. While make-on-demand libraries now exceed 75 billion enumerated molecules, their synthetic routes are dominated by a few reaction types, reducing diversity and inevitably leaving many interesting bioactive-like chemotypes unexplored. Here, we investigate the large-scale enumeration and targeted docking of isoquinuclidines.
View Article and Find Full Text PDFPhytomedicine
January 2025
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 15, Xi'an, Shaanxi, 710032, China. Electronic address:
Background: The pathogenesis of neuropathic pain is complex and lacks effective clinical treatment strategies. Medical plants and herbal extracts from traditional Chinese medicine with multi-target comprehensive effects have attracted great attention from scientists.
Purpose: To investigate the pharmacological active components and mechanism underlying the anti-neuralgia effect of classic analgesic formulas Duhuo Jisheng Mixture (DJM).
Adv Sci (Weinh)
January 2025
College of Forensic Medicine, Key Laboratory of National Health Commission for Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.
Lysine demethylase 7A (KDM7A) catalyzes the removal of dimethylation from histone H3 lysine 9 and lysine 27, both of which are associated with transcription repression. Previous study indicates that Kdm7a mRNA in the medial prefrontal cortex (mPFC) increases after drug exposure, yet its role in drug-related behaviors is largely unknown. In a morphine-conditioned place preference (CPP) paradigm, these findings reveal a specific increase of Kdm7a expression in the mPFC 7 days after drug withdrawal.
View Article and Find Full Text PDFJ Crit Care Med (Targu Mures)
October 2024
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
Opioids represent one of the key pillars in postoperative pain management, but their use has been associated with a variety of serious side effects. Thus, it is crucial to investigate the timing and course of opioid administration in order to ensure a best efficacy to side-effect profile. The aim of our article was to investigate the analgesic effects of locally administered morphine sulfate (intraplantar) in a carrageenan-induced inflammation model in rats.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), CEA, CNRS, Inserm, Service Hospitalier Frédéric Joliot, Université Paris-Saclay, Orsay, France. Electronic address:
Translational neuroimaging techniques are needed to address the impact of opioid tolerance on brain function and quantitatively monitor the impaired neuropharmacological response to opioids at the CNS level. A multiparametric PET study was conducted in rats. Rats received morphine daily to induce tolerance (15 mg/kg/day for 5 days), followed by 2-day withdrawal.
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