Identification of Mepenzolate Derivatives With Long-Acting Bronchodilatory Activity

Tanaka, Ken Ichiro; Yamakawa, Naoki; Yamashita, Yasunobu; Asano, Teita; Kanda, Yuki; Takafuji, Ayaka; Kawahara, Masahiro; Takenaga, Mitsuko; Fukunishi, Yoshifumi; Mizushima, Tohru

doi:10.3389/fphar.2018.00344

Cited by 4 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To further confirm that SCFAs regulates IL-1β-induced IL8 secretion via the GPR 109A receptor in H4 cells, an inhibitor of GPR 109A [0.2mM mepenzolate bromide (MB)] was used [23]. The results showed that SCFAs lost their anti-inflammatory effect on IL-1β-induced IL8 secretion in H4 cells (Fig 8).…”

Section: Scfas Lose Their Anti-inflammatory Effect On Il-1β-induced Imentioning

confidence: 85%

“…To investigate the function of HDAC3, HDAC5 and GPR109A in the SCFAs IL-1 β-induced inflammation in H4 cells, H4 cells were pretreated with the HDAC3 inhibitor TSA(100 nM), HDAC5 inhibitor LMK325 (100 nM) and 109A inhibitor mepenzolate bromide(MP) [23] (0.2 mM dissolved in DMSO) for 30 min before SCFAs (20 mM of acetate, propionate and butyrate) treatment for 30 min then exposed to 1ng/ml of recombinant human IL-1β (R&D Systems) for 24 h. Supernatants were collected and stored at -20˚C for ELISA IL8 analysis.…”

Section: Hdac Protein Assaymentioning

confidence: 99%

See 1 more Smart Citation

Short chain fatty acids produced by colonizing intestinal commensal bacterial interaction with expressed breast milk are anti-inflammatory in human immature enterocytes

et al. 2020

View full text Add to dashboard Cite

Necrotizing enterocolitis (NEC) is a devastating intestinal emergency that affects ten percent of very low birth weight premature babies and costs society in both expense and heartache. It is probably caused by an inappropriate interaction of colonizing bacteria with an immature intestine. A possible preventative measure is to feed prematures their mother's expressed breast milk in conjunction with a probiotic. This synbiotic prevention reduces the severity and incidence of this condition. This study was designed to determine the mechanism of the synbiotic effect in human and mouse fetal intestine. Breast milk interacting with a NEC preventative probiotic such as Bifidobacterium infantis can produce increased levels of short chain fatty acids (acetate, propionate and butyrate) (SCFAs). SCFAs are known to be anti-inflammatory in mature enterocytes and immunocytes. Very little is known about their role in immature intestine. When exposed to a human fetal cell line, fetal intestinal organoids and fetal mouse intestine, these SCFAs were anti-inflammatory. Their mechanism of antiinflammation differed from those reported for mature cells by involving the G-protein coupled receptor (GPR 109A) and inhibiting histone deacetylase 4 and 5. These bacterial metabolites may help explain the synbiotic anti-inflammatory effect of breast milk and probiotics given to premature infants at risk for NEC.

show abstract

Section: Scfas Lose Their Anti-inflammatory Effect On Il-1β-induced Imentioning

confidence: 85%

Section: Hdac Protein Assaymentioning

confidence: 99%

Short chain fatty acids produced by colonizing intestinal commensal bacterial interaction with expressed breast milk are anti-inflammatory in human immature enterocytes

et al. 2020

View full text Add to dashboard Cite

show abstract

Cholinergics/Anticholinergics

Griffith¹,

Dukat²

2021

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

This article covers classes of drugs and chemicals that act directly on muscarinic and nicotinic cholinergic receptors as agonists, antagonist, or allosteric modulators, together with an overview of the structures of muscarinic and nicotinic receptors. A brief history of the use of the small molecules muscarine, nicotine, and atropine to differentiate nicotinic and muscarinic receptors both of which respond to the neurotransmitter acetylcholine. This followed by discussion of the physical nature of the muscarinic G‐protein‐coupled‐receptor and the ligand‐gated‐ion‐channel nicotinic receptor. The structure–activity relationships of muscarinic agonists and antagonists are discussed with reference to attempts to develop of drugs selective for one of the five muscarinic receptors. Muscarinic antagonists are employed to treat disease states such as asthma, COPD, and overactive bladder. Muscarinic agonists have potential in the treatment of Alzheimer's disease. The structure–activity relationships of agonists and antagonists of nicotinic receptors are presented. Nicotinic agonists have been employed to assist in smoking cessation and have potential in treating Alzheimer's disease. Nicotinic antagonists have primarily been employed as neuromuscular blockers in surgery. The use of both positive and negative allosteric modulators of both muscarinic and nicotinic are discussed.

show abstract

Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity

Yamashita¹,

Tanaka

Yamakawa

et al. 2019

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

Identification of Mepenzolate Derivatives With Long-Acting Bronchodilatory Activity

Cited by 4 publications

References 24 publications

Short chain fatty acids produced by colonizing intestinal commensal bacterial interaction with expressed breast milk are anti-inflammatory in human immature enterocytes

Short chain fatty acids produced by colonizing intestinal commensal bacterial interaction with expressed breast milk are anti-inflammatory in human immature enterocytes

Cholinergics/Anticholinergics

Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity

Contact Info

Product

Resources

About