1.Pharmacology of bradykinin evoked coughing in guinea pigs.
Hewitt MM1, Adams G2, Mazzone SB3, Mori N2, Yu L4, Canning BJ5. J Pharmacol Exp Ther. 2016 Mar 21. pii: jpet.115.230383. [Epub ahead of print]
Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonist HOE 140. These cough responses rapidly desensitized, consistent with reports of B2 receptor desensitization. Bradykinin-evoked cough was potentiated by inhibition of both neutral endopeptidase and angiotensin converting enzyme (with thiorphan and captopril, respectively), but was largely unaffected by muscarinic or thromboxane receptor blockade (atropine and ICI 192605), cyclooxygenase or nitric oxide synthase inhibition (meclofenamic acid and L-NNA).
2.Histological changes caused by meclofenamic acid in androgen-independent prostate cancer tumors: evaluation in a mouse model.
Delgado-Enciso I1,2, Soriano-Hernández AD1, Rodriguez-Hernandez A1, Galvan-Salazar HR1,2, Montes-Galindo DA1, Martinez-Martinez R1, Valdez-Velazquez LL3, Gonzalez-Alvarez R1, Espinoza-Gómez F1, Newton-Sanchez OA1, Lara-Esqueda A4, Guzman-Esquivel J1,5. Int Braz J Urol. 2015 Sep-Oct;41(5):1002-7. doi: 10.1590/S1677-5538.IBJU.2013.00186.
Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity.
3.Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice.
Barrett JM1, Degenaar P2, Sernagor E1. Front Cell Neurosci. 2015 Aug 25;9:330. doi: 10.3389/fncel.2015.00330. eCollection 2015.
Retinitis pigmentosa (RP) is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC) hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA) was recently shown to diminish RGC hyperactivity and improve the signal-to-noise ratio (SNR) of RGC responses to light flashes and electrical stimulation in the rd10 mouse model of RP. We sought to extend these results to spatiotemporally patterned optogenetic stimulation in the faster-degenerating rd1 model and compare the effectiveness of a number of drugs known to disrupt rd1 hyperactivity. We crossed rd1 mice with a transgenic mouse line expressing the light-sensitive cation channel channelrhodopsin2 (ChR2) in RGCs, allowing them to be stimulated directly using high-intensity blue light.
4.Mefenamic acid in combination with ribavirin shows significant effects in reducing chikungunya virus infection in vitro and in vivo.
Rothan HA1, Bahrani H2, Abdulrahman AY3, Mohamed Z4, Teoh TC5, Othman S6, Rashid NN7, Rahman NA8, Yusof R9. Antiviral Res. 2016 Mar;127:50-6. doi: 10.1016/j.antiviral.2016.01.006. Epub 2016 Jan 18.
Chikungunya virus (CHIKV) infection is a persistent problem worldwide due to efficient adaptation of the viral vectors, Aedes aegypti and Aedes albopictus mosquitoes. Therefore, the absence of effective anti-CHIKV drugs to combat chikungunya outbreaks often leads to a significant impact on public health care. In this study, we investigated the antiviral activity of drugs that are used to alleviate infection symptoms, namely, the non-steroidal anti-inflammatory drugs (NSAIDs), on the premise that active compounds with potential antiviral and anti-inflammatory activities could be directly subjected for human use to treat CHIKV infections. Amongst the various NSAID compounds, Mefenamic acid (MEFE) and Meclofenamic acid (MECLO) showed considerable antiviral activity against viral replication individually or in combination with the common antiviral drug, Ribavirin (RIBA). The 50% effective concentration (EC50) was estimated to be 13 μM for MEFE, 18 μM for MECLO and 10 μM for RIBA, while MEFE + RIBA (1:1) exhibited an EC50 of 3 μM, and MECLO + RIBA (1:1) was 5 μM.