RILMENIDINE

Possibly Marketed Outside US

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

Molecular Formula	C10H16N2O
Molecular Weight	180.2468
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 2752		43.9 nM [Ki]
Alpha-2a adrenergic receptor 70 Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27265687	Agonist 2752		177.8 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16492616	Primary		Approved 8583	Tenaxum Approved Use Unknown

C_max

Value	Dose	Analyte	Population
3.49 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2782323/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.28 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
7.85 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.64 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.05 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.33 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.15 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
38.33 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2782323/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
38.61 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2782323/	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
78 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
8.51 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2782323/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.31 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2782323/	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
13 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
23 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
34 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2894159/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	RILMENIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1684749/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1684749/	Disc. AE: Dry mouth... AEs leading to discontinuation/dose reduction: Dry mouth (1.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/1684749/

AEs

AE	Significance	Dose	Population
Dry mouth	1.3% Disc. AE	2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1684749/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1684749/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 429 CYP2C19 2057 CYP1A2 2153	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI4OTQ4MCJ9fQ==	inconclusive [IC50 10 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI4OTQ4MCJ9fQ==	inconclusive [IC50 39.8107 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68712#section=Biological-Test-Results Page: 174.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDI4OTQ4MCJ9fQ==	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjg5NDgwIn19	yes [IC50 0.3981 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjg5NDgwIn19	yes [IC50 7.9433 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68712#section=Biological-Test-Results Page: 202 \| 211	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68712#section=Biological-Test-Results Page: 253.0

PubMed

Title	Date	PubMed
Improvement of cardiac diastolic function by long-term centrally mediated sympathetic inhibition in one-kidney, one-clip hypertensive rabbits.	2008-01	18091744
Inhibition of nischarin expression attenuates rilmenidine-evoked hypotension and phosphorylated extracellular signal-regulated kinase 1/2 production in the rostral ventrolateral medulla of rats.	2008-01	17940198
Impact of resistant starch on body fat patterning and central appetite regulation.	2007-12-12	18074032
Analysis of the role of central and peripheral alpha2-adrenoceptor subtypes in gastric mucosal defense in the rat.	2007-10	17707950
Possible role of NMDA receptors in antinociception induced by rilmenidine in mice in the formalin test.	2007-07	16934506
Centrally acting antihypertensive agents: an update.	2007-05	17485976
Direct evidence for imidazoline (I1) receptor modulation of ethanol action on norepinephrine-containing neurons in the rostral ventrolateral medulla in conscious spontaneously hypertensive rats.	2007-04	17374048
Contribution of imidazoline receptors and alpha2-adrenoceptors in the rostral ventrolateral medulla to sympathetic baroreflex inhibition by systemic rilmenidine.	2007-01	17143186
Involvement of phosphatidylcholine-selective phospholipase C in activation of mitogen-activated protein kinase pathways in imidazoline receptor antisera-selected protein.	2006-08-15	16598778
Effects of rilmenidine on 24-h rhythmicity of blood pressure and spontaneous baroreflex sensitivity in essential hypertensive subjects.	2006-08	16877965
Opposite to alpha2-adrenergic agonists, an imidazoline I1 selective compound does not influence reflex bradycardia in rabbits.	2006-07-30	16464646
Efficacy and tolerability of rilmenidine compared with isradipine in hypertensive patients with features of metabolic syndrome.	2006-07	16834827
Central adenosine signaling plays a key role in centrally mediated hypotension in conscious aortic barodenervated rats.	2006-07	16595736
How can we block sympathetic overactivity? Effects of rilmenidine and atenolol in overweight hypertensive patients.	2006-06	16543910
Nischarin as a functional imidazoline (I1) receptor.	2006-05-29	16678176
Reduced hemodynamic responses to physical and mental stress under low-dose rilmenidine in healthy subjects.	2006-04	16761192
Theoretical study of structure, pKa, lipophilicity, solubility, absorption, and polar surface area of some centrally acting antihypertensives.	2006-03-15	16263295
Centrally acting imidazolines stimulate vascular alpha 1A-adrenergic receptors in Rat-Tail Artery.	2006-01-06	16897362
Lipid-lowering actions of imidazoline antihypertensive agents in metabolic syndrome X.	2006-01	16416266
Rilmenidine--its antihypertensive efficacy, safety and impact on quality of life in perimenopausal women with mild to moderate essential hypertension.	2006	16492616
Cause and consequences of sympathetic hyperactivity in chronic kidney disease.	2006	16361848
Central actions of agmatine in conscious spontaneously hypertensive rats.	2005-11	16303638
Blockade of sympathetic nervous system activity by rilmenidine increases plasma adiponectin concentration in patients with essential hypertension.	2005-11	16280284
Role of imidazoline receptors in the anti-aversive properties of clonidine during opiate withdrawal in rats.	2005-10	16197523
Mitogen-activated protein kinase phosphorylation in the rostral ventrolateral medulla plays a key role in imidazoline (i1)-receptor-mediated hypotension.	2005-09	15901801
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.	2005-07	15965355
Site-dependent inhibition of neuronal c-jun in the brainstem elicited by imidazoline I1 receptor activation: role in rilmenidine-evoked hypotension.	2005-05-09	15910806
Noradrenergic modulation of XII motoneuron inspiratory activity does not involve alpha2-receptor inhibition of the Ih current or presynaptic glutamate release.	2005-04	15579572
Clinical evidence for drug treatments in obesity-associated hypertensive patients--a discussion paper.	2005-03	15834464
Rat clonidine mydriasis model: imidazoline receptors are not involved.	2005-01-15	15620566
Comparison of rilmenidine and lisinopril on ambulatory blood pressure and plasma lipid and glucose levels in hypertensive women with metabolic syndrome.	2005-01	15881482
Rilmenidine prevents blood pressure increase in rats with compromised nitric oxide production.	2004-12	15569409
[Rilmenidine sympatholytic activity preserves mental and orthostatic sympathetic response and epinephrine secretion].	2004-10-28	15506067
Effects of centrally acting antihypertensive drugs on the microcirculation of spontaneously hypertensive rats.	2004-10	15448876
Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.	2004-10	15145918
Imidazoline binding sites and their ligands: an overview of the different chemical structures.	2004-09	15224384
[The effects of rilmenidine on cardiac autonomic function in healthy volunteers].	2004-08	15282063
Rilmenidine sympatholytic activity preserves mental stress, orthostatic sympathetic responses and adrenaline secretion.	2004-08	15257176
Effects of rilmenidine on proximal tubular fluid absorption in rats.	2004-06-12	15191410
Pharmacokinetic/pharmacodynamic assessment of tolerance to central nervous system effects of a 3 mg sustained release tablet of rilmenidine in hypertensive patients.	2004-06	15260911
LNP 906, the first high-affinity photoaffinity ligand selective for I1 imidazoline receptors.	2004-06	15178642
Moxonidine and rilmenidine injected into the medial septal area reduces the salivation induced by pilocarpine.	2004-05-31	15233928
The effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine, and antagonists yohimbine and efaroxan, on the spinal cholinergic receptor system in the rat.	2004-04	15078339
Chronic treatment with rilmenidine in spontaneously hypertensive rats: differences between two schedules of administration.	2004-03	15076223
[Case report: hypertension after stroke].	2004	15346547
[Effect of rilmenidine on intraocular pressure in rabbits, interaction with efaroxan and rauwolscine].	2004	15218755
Efficacy and tolerability of long-term rilmenidine treatment in hypertensive diabetic patients. A retrospective analysis of a general practice study.	2004	15134471
Elevated sympathetic activity may promote insulin resistance syndrome by activating alpha-1 adrenergic receptors on adipocytes.	2004	15082116
Apparent absence of direct renal effect of imidazoline receptor agonists.	2003-12	15028602
[Effect of Rilmenidine(Tenaxum) on the activity of the autonomic nervous system in patients with hypertension and asthma].	2003	15058158

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:47:33 GMT 2025` Edited by `admin` on `Mon Mar 31 18:47:33 GMT 2025`
Record UNII	P67IM25ID8
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

HYPERIUM

Preferred Name

English

RILMENIDINE

Official 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