NFEPP(NFEPP) - 药物靶点：μ opioid receptor_在研适应症：结肠炎_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

μ opioid receptor

作用方式

激动剂

作用机制

μ opioid receptor激动剂(μ-阿片受体激动剂)

治疗领域

消化系统疾病

在研适应症

结肠炎

非在研适应症-

原研机构

Queen's University

在研机构

Queen's University

非在研机构-

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 NFEPP 相关的临床结果

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100 项与 NFEPP 相关的转化医学

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100 项与 NFEPP 相关的专利（医药）

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11

项与 NFEPP 相关的文献（医药）

2025-11-01·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Preparation of highly-dispersed iron pyrophosphate nanoparticles via ultrasound-assistant carboxymethyl cellulose modification to enhance their liposome encapsulation and cell absorption

Article

作者: Gao, Wei ; Li, Yang ; Wei, Yun-Shan ; Liu, Kun-Lun

Ferric pyrophosphate (FePP) is commonly used in fortified foods because of its subtle metallic odor/color. However, the insoluble nature of FePP restricts its intestinal absorption, thereby diminishing its efficacy. Liposomes can enhance the transmembrane absorption of encapsulated ingredients but encounter difficulties when encapsulating insoluble compounds. In this study, it was initially attempted to boost FePP solubility by reducing its particle size. Nevertheless, nanoscale FePP (N-FePP) exhibited a strong tendency to aggregate. To address this, an ultrasound-assisted carboxymethyl cellulose modification was innovatively proposed. This method effectively prevented N-FePP aggregation by increasing its charge density from -23 mV to -40 mV and decreasing surface tension of the N-FePP suspension from 71.1 mN/m to 43.8 mN/m. Consequently, the modified N-FePP (MN-FePP), with a particle size of 237 nm and excellent dispersion, was successfully obtained. The encapsulation efficiency of MN-FePP in liposomes (MN-FePP-Lip) was significantly enhanced compared to that of N-FePP (74.9 % vs. 27.8 %). Furthermore, in comparation with the unencapsulated MN-FePP, MN-FePP-Lip exhibited increased cellular absorption efficiency (intracellular iron concentrations of 171.54 μmol/L vs. 115.24 μmol/L) and total antioxidant levels (9.04 U/mg prot vs. 7.28 U/mg prot) in cells. Therefore, the MN-FePP-Lip developed in this study shows great potential as a novel iron fortifier.

2025-02-01·British Journal of Pharmacology

A pH‐sensitive opioid does not exhibit analgesic tolerance in a mouse model of colonic inflammation

Article

作者: Schincariol, Hailey ; Stein, Christoph ; Lomax, Alan E. ; Vanner, Stephen J. ; Reed, David E. ; Jiménez‐Vargas, Nestor Nivardo ; Guzman‐Rodriguez, Mabel ; Tsang, Quentin ; Degro, Claudius E. ; Bunnett, Nigel W.

Abstract:

Background and Purpose:

Tolerance to the analgesic effects of opioids and resultant dose escalation is associated with worsening of side effects and greater addiction risk. Here, we compare the development of tolerance to the conventional opioid fentanyl with a novel pH‐sensitive μ‐opioid receptor (MOR) agonist, (±)‐N‐(3‐fluoro‐1‐phenethylpiperidine‐4‐yl)‐N‐phenyl propionamide (NFEPP) that is active only in acidic inflammatory microenvironments.

Experimental Approach:

An opioid tolerance model was developed in male C57BL/6 mice, with and without dextran sulphate sodium colitis, using increasing doses of either fentanyl or NFEPP over 5 days. Visceral nociception was assessed in vivo by measuring visceromotor responses (VMRs) to noxious colorectal distensions and in vitro measuring colonic afferent nerve activity of mesenteric nerves and performing patch‐clamp recordings from isolated dorsal root ganglia neurons. Somatic thermal nociception was tested using a tail immersion assay. Cardiorespiratory effects were analysed by pulse oximeter experiments.

Key Results:

VMRs and tail immersion tests demonstrated tolerance to fentanyl, but not to NFEPP in colitis mice. Cross‐tolerance also occurred to fentanyl, but not to NFEPP. The MOR agonist DAMGO inhibited colonic afferent nerve activity in colitis mice exposed to chronic NFEPP, but not those from fentanyl‐treated mice. Similarly, in patch‐clamp recordings from isolated dorsal root ganglia neurons, DAMGO inhibited neurons from NFEPP‐, but not fentanyl‐treated mice.

Conclusion and Implications:

NFEPP did not exhibit tolerance in an inflammatory pain model, unlike fentanyl. Consequently, dose escalation to maintain analgesia during an evolving inflammation could be avoided, mitigating the potential risk of side effects.

2024-09-01·NEUROPHARMACOLOGY

Assessment of the antinociceptive, respiratory-depressant, and reinforcing effects of the low pKa fluorinated fentanyl analogs, FF3 and NFEPP

Article

作者: Brackeen, Marcus F ; Howell, Grace H ; Cowart, Kristian ; Haskell, Jacob P ; Freeman, Kevin B ; Edwards, Shelley R ; Huskinson, Sally L ; Rowlett, James K ; Araujo, Aaron A ; Blough, Bruce E

RATIONALE:

Recent studies report that fentanyl analogs with relatively low pK_a values produce antinociception in rodents without other mu opioid-typical side effects due to the restriction of their activity to injured tissue with relatively low pH values. However, it is unclear if and to what degree these compounds may produce mu opioid-typical side effects (respiratory depression, reinforcing effects) at doses higher than those required to produce antinociception.

OBJECTIVES:

The present study compared the inflammatory antinociceptive, respiratory-depressant, and reinforcing effects of fentanyl and two analogs of intermediate (FF3) and low (NFEPP) pK_a values in terms of potency and efficacy in male and female Sprague-Dawley rats.

METHODS:

Nociception was produced by administration of Complete Freund's Adjuvant into the hind paw of subjects, and antinociception was measured using an electronic Von Frey test. Respiratory depression was measured using whole-body plethysmography. Reinforcing effects were measured in self-administration using a progressive-ratio schedule of reinforcement. The dose ranges tested for each drug encompassed no effect to maximal effects.

RESULTS:

All compounds produced full effects in all measures but varied in potency. FF3 and fentanyl were equipotent in antinociception and self-administration, but FF3 was less potent than fentanyl in respiratory depression. NFEPP was less potent than fentanyl in every measure. The magnitude of potency difference between antinociception and other effects was greater for FF3 than for NFEPP or fentanyl, indicating that FF3 had the widest margin of safety when relating antinociception to respiratory-depressant and reinforcing effects.

CONCLUSIONS:

Low pK_a fentanyl analogs possess potential as safer analgesics, but determining the optimal degree of difference for pK_a relative to fentanyl will require further study due to some differences between the current results and findings from prior work with these analogs.

100 项与 NFEPP 相关的药物交易

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