Effect of Fenspiride, a Non-steroidal Antiinflammatory Agent, on Neurogenic Mucus Secretion in Ferret Trachea in Vitro

Khawaja, Aamir M; Liu, Y.-C.; Rogers, Duncan F.

doi:10.1006/pupt.1999.0221

Cited by 10 publications

(4 citation statements)

References 17 publications

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“…It is an H1-antihistamine agent that decreases the synthesis of pro-inflammatory mediators (cytokines, tumor necrosis factor α (TNF-α), prostaglandins, leukotrienes, and free radicals) and relaxes the smooth muscles, similarly to papaverine. [8][9][10] The presence of H1-histamine receptors on both osteoblasts and osteoclasts has been confirmed. 11 Pro-inflammatory cytokines, e.g., interleukin-1, interleukin-6 and TNF-α, increase osteoclast activity through the RANK/RANKL/OPG pathway and inhibit osteoblast activity.…”

mentioning

confidence: 72%

Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats

Matuszewska¹,

Nowak²,

Jędrzejuk³

et al. 2019

Adv Clin Exp Med

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et al. Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats. AbstractBackground. Fenspiride is an antagonist of H1-histamine receptors that is used to treat acute and chronic respiratory tract infections and otitis media in children and adolescents.Objectives. The aim of the study was to assess the influence of long-term administration of fenspiride on bone mineral density (BMD) and bone turnover in young growing rats.Material and methods. The experiment was carried out on 18 young (8-week-old) male Wistar rats receiving either fenspiride 15 mg/kg intragastrically (ig) (group F) or saline solution 4 mL/kg ig (group C) for 3 months. On days 1 and 93, blood samples were collected and serum levels of calcium, phosphorus and markers of bone turnover were measured. On days 2 and 92, BMD was measured with dual-energy X-ray absorptiometry (DXA) using small animal software. Results.We detected no influence of fenspiride on weight gain, total body BMD (0.212 ±0.010 g/cm 2 vs 0.204 ±0.024 g/cm 2 ), hind limb BMD (0.264 ±0.016 g/cm 2 vs 0.252 ±0.027 g/cm 2 ), or bone macroscopic parameters. There were no significant differences between group F and group C in serum levels of osteocalcin (group F: 0.42 ±0.09 ng/mL vs group C: 0.43 ±0.08 ng/mL), C-terminal telopeptide of type I collagen (F: 0.31 ±0.08 ng/mL vs C: 0.29 ±0.08 ng/mL), osteoprotegerin (F: 5.47 ±0.78 pg/mL vs C: 5.35 ±1.65 pg/mL), receptor activator of nuclear factor kappa B ligand (F: 0.65 ±0.85 pg/mL vs C: 0.56 ±0.86 pg/mL), parathormone (F: 237 ±182 pg/mL vs C: 289 ±200 pg/mL), total calcium (F: 6.38 ±1.50 mg/dL vs C: 6.83 ±1.71 mg/dL), or inorganic phosphorus (F: 5. 19 ±1.76 mg/dL vs C: 5.50 ±1.32 mg/dL). Conclusions.Long-term administration of fenspiride has no negative impact on BMD and bone metabolism in young growing rats.

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confidence: 72%

Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats

Matuszewska¹,

Nowak²,

Jędrzejuk³

et al. 2019

Adv Clin Exp Med

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“…Фенспирид также подавлял секрецию, вызванную ацетилхолином, но не угнетал секрецию, индуциро ванную субстанцией P. Антагонисты гистаминовых рецепторов увеличивали базальную секрецию на 164 %, тогда как фенспирид не нарушал базальной секреции. Авторы сделали вывод о том, что in vitro в исследовании на трахее хорька фенспирид подавлял неврально опосредованную секрецию слизи, а наи более вероятным объяснением был антимускарино вый эффект, хотя не обязательно этот механизм был единственным [19].…”

Section: экспериментальные исследованияunclassified

Antiinflammatory drug fenspirid

Visel¹,

Visel²,

Pronina³

2007

Pulʹmonologiâ (Mosk.)

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“…Both the rate and degree or co-ordination of ciliary beating can be measured [26]. There are in vitro methods to measure mucus production, either by direct assay of mucus levels in the extracellular medium or by direct monitoring of degranulation events from either native tissue or cell lines [27,28]. Finally, the Ussing chamber technique [29] can be used to monitor ion transport across the airway epithelium, again using native tissues or epithelial cell lines grown to confluence on a permeable support.…”

Section: Respiratory Systemmentioning

confidence: 99%

The application of in vitro methods to safety pharmacology

Wakefield

Pollard

Redfern

et al. 2002

Fundamemntal Clinical Pharma

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The ICH S7A guideline defines safety pharmacology (SP) studies as those that investigate 'the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above', and permits both in vivo and in vitro techniques, as appropriate. The implementation of these ICH guidelines by the pharmaceutical industry--whilst providing a welcome and long overdue clarity into the scientific rationale, timing and regulatory requirements for SP studies--has also generated new challenges, both logistical and scientific, which have a major impact on drug development. These factors have motivated us to consider the introduction of in vitro techniques at an early stage of SP evaluation. Amongst these factors are: the expanded range of study types and physiological parameters to be assessed, the increased 'front-loading' of SP at earlier stages of the drug discovery process; the greater number of new chemical entities (NCEs) to be tested, together with limited compound supply; the condensed time frames for drug development, the higher and quicker throughput of in vitro vs. in vivo tests; the increasing predictability of in vitro tests and application of the '3Rs' rule of animal welfare (reduction, replacement and refinement). Also, there is the failure of traditional in vivo safety evaluation to predict certain clinical side-effects. The use of molecular (e.g. fluorescence and cloned ion channel), cellular (e.g. patch clamp and isolated cardiac cells) and tissue-based (e.g. microelectrodes and Purkinje fibres) methods offers a wide portfolio of novel techniques for SP evaluation of NCEs at a pre-in vivo stage. Thus, innovative in vitro techniques will contribute significantly to the early SP evaluation of NCEs.

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Effect of Fenspiride, a Non-steroidal Antiinflammatory Agent, on Neurogenic Mucus Secretion in Ferret Trachea in Vitro

Cited by 10 publications

References 17 publications

Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats

Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats

Antiinflammatory drug fenspirid

The application of in vitro methods to safety pharmacology

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