Delving into the Latest Updates on Amiloride Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

3,5-diamino-N-carbamimidoyl-6-chloropyrazine-2-carboxamide, Amiloride, Amiloride hydrochloride (USP)

+ [9]

Target

ENaCα

Mechanism

ENaCα inhibitors(sodium channel epithelial 1 subunit alpha inhibitors)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Heart FailureHypertension

Inactive Indication-

Originator Organization

Perrigo Co. Plc

Active Organization

Padagis US LLC

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (05 Oct 1981),

Heart FailureHypertension

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC6H13Cl2N7O3

InChIKeyLTKVFMLMEYCWMK-UHFFFAOYSA-N

CAS Registry17440-83-4

Resistant hypertension is defined as blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes including diuretics. Patients with resistant hypertension has at least 1.5-fold higher cardiovascular risk than those with non-resistant hypertension. Therefore, controlling blood pressure is crucial in patients with resistant hypertension.
It has been unclear which antihypertensive agent should be added in patients who cannot reach target blood pressure despite use of three antihypertensive agents. There have been three randomized clinical trials that proved the efficacy of spironolactone in resistant hypertension, but they were small sized, comparison study to placebo. Recently published PATHWAY-2 study which compared the efficacy of spironolactone with placebo, doxazosin, and bisoprolol showed superiority of spironolactone in blood pressure lowering in patients with resistant hypertension. Thus, revised ACC/AHA and ESC/ESH guideline for arterial hypertension recommended spironolactone as the fourth agent for resistant hypertension. However, in real world, adherence to spironolactone may not be adequate because of adverse effect such as gynecomastia, hyperkalemia, and so on.
Recently, sub-study of PATHWAY-2 revealed that amiloride changes systolic blood pressure by -22.2 mmHg (95% CI, -24.7 to -19.7) which is comparable with the effect of spironolactone (-21.8 mmHg; 95% CI, -24.2 to -19.3). However, it was not randomized clinical trial to compare the effect between spironolactone and amiloride in patients with resistant hypertension.
This study aims to compare the effect of spironolactone and amiloride on home blood pressure in resistant hypertensive patients and to compare the rate of target blood pressure achievement between spironolactone and amiloride in resistant hypertensive patients.

Start Date16 Nov 2020

Sponsor / Collaborator

Yonsei University

100 Clinical Results associated with Amiloride Hydrochloride

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100 Translational Medicine associated with Amiloride Hydrochloride

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100 Patents (Medical) associated with Amiloride Hydrochloride

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7,834

Literatures (Medical) associated with Amiloride Hydrochloride

01 Dec 2024·BURNS

Topical application of anti-inflammatory agents on burn wounds and their effect on healing

Article

Author: Varon, David E. ; Nuutila, Kristo ; Chan, Rodney ; Chan, Christopher K ; Neelon, Jamie ; Smithson, Steven Blake ; Carlsson, Anders H ; Varon, David E ; Chan, Rodney K. ; Carlsson, Anders H. ; Chan, Rodney K ; Chan, Christopher K. ; Yau, Irene

Advancements in the treatment of burns have considerably improved overall survival rates, but they have also highlighted several long-term sequelae related to the injury. Hypertrophic scars can impair function, reduce quality of life, and require multiple procedures as well as physical therapy. The purpose of this study was to investigate the effects of topical application of anti-inflammatory drugs in the treatment of burns. Up to 15 deep-partial thickness burns were created on the dorsum of four anesthetized swine. Subsequently, the burn wounds were randomized to receive amiloride, celecoxib, dexamethasone or minocycline mixed in a hydrogel. Silver sulfadiazine cream and blank hydrogel acted as controls. The animals were followed for 90 days and the wounds were assessed on days 3, 7, 14, 28 and 90 post-burn. Assessments were performed using photographs (macroscopic healing, contraction), laser-speckle imaging (blood perfusion), 3D camera (scarring, pigmentation), and histology (inflammation, burn depth, epidermal maturation). Inflammation was present in all burn wound histology specimens and peaked on day 7 in all groups. Regardless of the treatment the burns progressed and were deeper on day 7 in comparison to day 3. The burns were 50 - 80 % healed by day 14, but no significant differences were observed. No differences in epidermal thickness, rete ridges, contraction, hypopigmentation, or scar elevation were seen on day 90. Topical anti-inflammatories did not significantly decrease inflammation or mitigate burn wound progression in deep partial thickness burns in pigs. Also, no significant differences in wound healing or quality of healing were observed.

01 Dec 2024·JOURNAL OF HAZARDOUS MATERIALS

Accumulation of nanoplastics by wheat seedling roots: Both passive and energy-consuming processes

Article

Author: Yang, Qian ; Zhou, Wenhui ; Zhu, Jiahui ; Sun, Yilei ; He, Yuan ; Zhan, Xinhua ; Zheng, Qiuping

Nanoplastics can transfer from the environment to plants and potentially harm organisms. However, the mechanisms on how crop root systems absorb and transport nanoplastics are still unclear. Here, original and fluorescent labeled polystyrene and polyvinyl chloride nanoparticles (PS-NPs, PVC-NPs; 30 nm; 10 mg L^-1) were employed to study the distribution and internalization pathways in wheat seedling roots. In the study, nanoplastics accumulated more in the root tip and surface, with PVC-NPs more prevalent than PS-NPs. After being treated with inhibitors (Na₃VO₄, chlorpromazine and amiloride), the nanoplastics mean fluorescence intensities were reduced by 4.0-51.1 %. During the uptake, both passive and energy-consuming pathways occurred. For the energy-consuming uptake pathway, macropinocytosis contributed more to cytoplasm than clathrin-mediated endocytosis. H⁺ influx was observed during nanoplastic transport into the cytoplasm, and the reduction in plasma membrane ATPase activity led to a decrease in nanoplastic internalization. These results elucidate the pathways of nanoplastics absorption and transport in wheat roots, provide crucial evidence for assessing nanoplastics' ecological risks and support the development of technologies to block nanoplastics absorption by crop roots, ensuring agricultural and ecosystem safety.

20 Nov 2024·JOURNAL OF NEUROSCIENCE

Acid-Sensing Ion Channels Drive the Generation of Tactile Impulses in Merkel Cell–Neurite Complexes of the Glabrous Skin of Rodent Hindpaws

Article

Author: Ling, Jennifer ; Yamada, Ayaka I ; Gu, Jianguo G. ; Yamada, Akihiro ; Gautam, Mayank ; Gu, Jianguo G ; Luo, Wenqin ; Yamada, Ayaka I. ; Gupta, Saurav ; Furue, Hidemasa

Merkel cell–neurite complexes (MNCs) are enriched in touch-sensitive areas, including whisker hair follicles and the glabrous skin of the rodent's paws, where tactile stimulation elicits slowly adapting type 1 (SA1) tactile impulses to encode for the sense of touch. Recently, we have shown with rodent whisker hair follicles that SA1 impulses are generated through fast excitatory synaptic transmission at MNCs and driven by acid-sensing ion channels (ASICs). However, it is currently unknown whether, besides whisker hair follicles, ASICs also play an essential role in generating SA1 impulses from MNCs of other body parts in mammals. In the present study, we attempted to address this question by using the skin–nerve preparations made from the hindpaw glabrous skin and tibial nerves of both male and female rodents and applying the pressure-clamped single–fiber recordings. We showed that SA1 impulses elicited by tactile stimulation to the rat hindpaw glabrous skin were largely diminished in the presence of amiloride and diminazene, two ASIC channel blockers. Furthermore, using the hindpaw glabrous skin and tibial nerve preparations made from the mice genetically deleted of ASIC3 channels (ASIC3−/−), we showed that the frequency of SA1 impulses was significantly lower in ASIC3−/−mice than in littermate wild-type ASIC3+/+mice, a result consistent with the pharmacological experiments with ASIC channel blockers. Our findings suggest that ASIC channels are essential for generating SA1 impulses to underlie the sense of touch in the glabrous skin of rodent hindpaws.

100 Deals associated with Amiloride Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D00649	Amiloride Hydrochloride	C03DB01	DB00594

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Heart Failure	US	Padagis US LLC	05 Oct 1981
Hypertension	US	Padagis US LLC	05 Oct 1981

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02522650 (Pubmed \| Am J Nephrol)	Phase 4	Kidney Diseases	12	Amiloride 5 mg	ijinyeqdzs(lnvnqyafbl) = ntjepwyzfb iqjicdxybt (pgxngrypir )	-	06 May 2021
				Triamterene 50 mg	ijinyeqdzs(lnvnqyafbl) = dbbywfdwcq iqjicdxybt (pgxngrypir )
NCT01910259 (MS-SMART, ECTRIMS2020)	Phase 2	Multiple Sclerosis, Secondary Progressive	108	Fluoxetine	-	-	07 Dec 2020
				Riluzole
ASN2020	Not Applicable	Urolithiasis	31	Amiloride	phvcvqtmax(gdxnanferd) = Three (20%) patients stopped due to delayed intolerance and 2 (13%) due to elevated urinary calcium ubqkpwvhce (vbqavvbxit ) View more	Negative	19 Oct 2020
				Thiazide
ASN2020	Not Applicable	Kidney Diseases	12	Amiloride 5 mg	kzldkovdfp(yzlnhlljhq) = Three patients exited the study due to hyperkalemia tvggxszrxv (gyfvfizths )	Positive	19 Oct 2020
				Triamterene 50 mg
NCT01733680 (CTgov)	Early Phase 1	Attention Deficit Disorder With Hyperactivity	3	Behavioral+amiloride (Amiloride)	xzevafaofq(hxeehpgkrd) = iqwedohetr uxwbqdekho (jupkjitojy, ddqqndafoq - jvddyvabqr) View more	-	20 Jul 2018
				Behavioral (Placebo)	xzevafaofq(hxeehpgkrd) = zvcrjrxoaa uxwbqdekho (jupkjitojy, owhtrpxrok - cjpjtexwws) View more
ESC2016	Not Applicable	Coronary Disease	-	Amiloride HCl Dihydrate	rpvzadrriu(bfvzlkfkmn) = gqdkaivdkg zsogncvpqq (cmopknoawi )	-	30 Aug 2016
ASN2015	Not Applicable	Hypokalemia \| Gitelman Syndrome SLC12A3 gene	-	Spironolactone	pfihvltbwe(ukkiclxphw) = bqvpiwgdju nmpccsglcf (hhqojsoumh ) View more	Positive	03 Nov 2015
				Amiloride	pfihvltbwe(ukkiclxphw) = thgxowigyg nmpccsglcf (hhqojsoumh ) View more
SP309 (ERA2015)	Not Applicable	Kidney Diseases urine albumin-to-creatinine ratio (ACR)	21	Spironolactone	mojkospvsk(nzelxihyut) = awflnwurek sqbczigmfd (moovtivhdz, -21% - -47.9%)	Positive	21 May 2015
				Hydrochlorothiazide	mojkospvsk(nzelxihyut) = qwtgkwwacn sqbczigmfd (moovtivhdz, -28.1% - -56.9%)
NCT01308983 (Pubmed \| J Clin Hypertens (Greenwich))	Not Applicable	-	17	Amiloride	jcauqopetk(pyqsrppxiy) = dhptcitpck swnpcmdymk (bepzzboofw ) View more	-	01 Jan 2014
ASN2013	Not Applicable	Renal interstitial fibrosis	-	Amiloride	oepgkwgymi(zyigytkwsd) = nncwhsaalb smknajmjrz (xslumzbrnn )	Positive	05 Nov 2013
				Lithium alone	oepgkwgymi(zyigytkwsd) = ktzejypzur smknajmjrz (xslumzbrnn )