RILMENIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H16N2O
Molecular Weight	180.2468
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1CC1C(NC2=NCCO2)C3CC3

InChI

InChIKey=CQXADFVORZEARL-UHFFFAOYSA-N

InChI=1S/C10H16N2O/c1-2-7(1)9(8-3-4-8)12-10-11-5-6-13-10/h7-9H,1-6H2,(H,11,12)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11721891
Curator's Comment: description was created based on several sources, including https://www.drugs.com/international/rilmenidine.html | https://clinicaltrials.gov/ct2/show/NCT00892892 | https://www.ncbi.nlm.nih.gov/pubmed/16492616 | https://www.ncbi.nlm.nih.gov/pubmed/25542610 | http://agence-prd.ansm.sante.fr/html/par_eu/20110201_fr462_rilmenidine_pl.pdf

Rilmenidine (brand names Albarel, Hyperium, Iterium and Tenaxum) is an imidazoline derivative used for the treatment of hypertension. Rilmenidine, an oxazoline compound with antihypertensive properties, acts on both medullary and peripheral vasomotor structures. Rilmenidine shows greater selectivity for imidazoline receptors than for cerebral alpha2-adrenergic receptors, distinguishing it from reference alpha2-agonists. Rilmenidine is as effective in monotherapy as all other first line classes of drugs, including diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and calcium antagonists. It is well tolerated and can be taken in combination for greater efficacy. Sedation and dry mouth are not prominent side effects and withdrawal hypertension is not seen when treatment is stopped abruptly. In addition to a reduction in blood pressure, Rilmenidine has been shown to improve glucose tolerance, lipid risk factors, and insulin sensitivity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nischarin 7 Target ID: CHEMBL3923 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12065769	Agonist 2678		43.9 nM [Ki]
Alpha-2a adrenergic receptor 63 Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27265687	Agonist 2678		177.8 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16492616	Primary		Approved 8429	Tenaxum Approved Use Unknown

PubMed

Title	Date	PubMed
Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension?	2001	14728014
Interactions of ligands at angiotensin II-receptors and imidazoline receptors.	2001 Feb	11286399
Update on rilmenidine: clinical benefits.	2001 Nov	11721891
I1 receptors, cardiovascular function, and metabolism.	2001 Nov	11721890
Sympathetic nervous system and insulin resistance: from obesity to diabetes.	2001 Nov	11721888
Involvement of imidazoline receptors in the baroreflex effects of rilmenidine in conscious rabbits.	2001 Sep	11564982
Effects of rilmenidine and guanfacine in acute renal denervated rats.	2002	12434513
[Efficacy and tolerance of rilmenidine in patients with mild to moderate hypertension. Results of a Czech and Slovak 6-month multicenter study].	2002 Aug	12425202
Imidazoline antihypertensive drugs: a critical review on their mechanism of action.	2002 Jan	11916539
Sympathetic modulation of renal blood flow by rilmenidine and captopril: central vs. peripheral effects.	2002 Jan	11739119
Evidence for synergy between alpha(2)-adrenergic and nonadrenergic mechanisms in central blood pressure regulation.	2002 Mar 5	11877365
Protective effects of rilmenidine and AGN 192403 on oxidative cytotoxicity and mitochondrial inhibitor-induced cytotoxicity in astrocytes.	2002 Nov 15	12419464
Concentration-effect relationships of two rilmenidine single-dose infusion rates in hypertensive patients.	2002 Oct	12386644
[Effect of Rilmenidine(Tenaxum) on the activity of the autonomic nervous system in patients with hypertension and asthma].	2003	15058158
Protective effects of centrally acting sympathomodulatory drugs on myocardial ischemia induced by sympathetic overactivity in rabbits.	2003 Jan	12532231
Effect of ethanol on reductions in norepinephrine electrochemical signal in the rostral ventrolateral medulla and hypotension elicited by I1-receptor activation in spontaneously hypertensive rats.	2003 Sep	14506409
Chronic ethanol administration attenuates imidazoline I1 receptor- or alpha 2-adrenoceptor-mediated reductions in blood pressure and hemodynamic variability in hypertensive rats.	2004 Feb 6	14757148
Sympathetic responses to stress and rilmenidine in 2K1C rabbits: evidence of enhanced nonvascular effector mechanism.	2004 Mar	14744928
Noradrenergic modulation of XII motoneuron inspiratory activity does not involve alpha2-receptor inhibition of the Ih current or presynaptic glutamate release.	2005 Apr	15579572
Comparison of rilmenidine and lisinopril on ambulatory blood pressure and plasma lipid and glucose levels in hypertensive women with metabolic syndrome.	2005 Jan	15881482
Rat clonidine mydriasis model: imidazoline receptors are not involved.	2005 Jan 15	15620566
Neuronal norepinephrine responses of the rostral ventrolateral medulla and nucleus tractus solitarius neurons distinguish the I1- from the alpha2-receptor-mediated hypotension in conscious SHRs.	2005 Jul	15965355
Clinical evidence for drug treatments in obesity-associated hypertensive patients--a discussion paper.	2005 Mar	15834464
Site-dependent inhibition of neuronal c-jun in the brainstem elicited by imidazoline I1 receptor activation: role in rilmenidine-evoked hypotension.	2005 May 9	15910806
Role of imidazoline receptors in the anti-aversive properties of clonidine during opiate withdrawal in rats.	2005 Oct	16197523
Mitogen-activated protein kinase phosphorylation in the rostral ventrolateral medulla plays a key role in imidazoline (i1)-receptor-mediated hypotension.	2005 Sep	15901801
Cause and consequences of sympathetic hyperactivity in chronic kidney disease.	2006	16361848
Reduced hemodynamic responses to physical and mental stress under low-dose rilmenidine in healthy subjects.	2006 Apr	16761192
Lipid-lowering actions of imidazoline antihypertensive agents in metabolic syndrome X.	2006 Jan	16416266
Opposite to alpha2-adrenergic agonists, an imidazoline I1 selective compound does not influence reflex bradycardia in rabbits.	2006 Jul 30	16464646
Impact of resistant starch on body fat patterning and central appetite regulation.	2007 Dec 12	18074032
Analysis of the role of central and peripheral alpha2-adrenoceptor subtypes in gastric mucosal defense in the rat.	2007 Oct	17707950

Patents

Sample Use Guides

In Vivo Use Guide

1 mg/day, up to 2 mg/day in divided doses

Route of Administration: Oral

In Vitro Use Guide

The cytotoxic activity of rilmenidine and doxorubicin on K562 cells was measured using the MTT assay. After treatment in 96-well plates, MTT solution (3-(4,5-dimethylthiazol-2-yl)-2,5-dyphenyl tetrazolium bromide) (20 μL/well) was added to each well. Sampleswere incubated for a further 4 h, followed by the addition of 100 μl of 10% SDS. Absorbance at 570 nmwasmeasured the next day.

Name

Type

Language

RILMENIDINE

Official Name

English

HYPERIUM

Brand Name

English

Rilmenidine [WHO-DD]

Common Name

English

rilmenidine [INN]

Common Name

English

RILMENIDINE [MI]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC02AC06