Rilmenidine hemifumarate | CAS# 207572-68-7 | I1-imidazoline binding site selective ligand | α2-adrenoceptor agonist

MedKoo Cat#: 574387 | Name: Rilmenidine hemifumarate

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Rilmenidine hemifumarate is an I1-imidazoline binding site selective ligand and α2-adrenoceptor agonist that possesses greater I1 vs α2 selectivity than the prototypical compound, clonidine. This product is thought to enhance autophagy and has been shown to increase LC3-II levels in PC12 cells.

Chemical Structure

Rilmenidine hemifumarate

CAS#207572-68-7

Theoretical Analysis

MedKoo Cat#: 574387

Name: Rilmenidine hemifumarate

CAS#: 207572-68-7

Chemical Formula: C24H36N4O6

Exact Mass: 0.0000

Molecular Weight: 476.57

Elemental Analysis: C, 60.49; H, 7.61; N, 11.76; O, 20.14

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
1g	USD 3,850.00	2 Weeks

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Synonym

Rilmenidine hemifumarate

IUPAC/Chemical Name

N-(dicyclopropylmethyl)-4,5-dihydrooxazol-2-amine hemifumarate

InChi Key

LZFATBMLSYHRTC-WXXKFALUSA-N

InChi Code

InChI=1S/2C10H16N2O.C4H4O4/c2*1-2-7(1)9(8-3-4-8)12-10-11-5-6-13-10;5-3(6)1-2-4(7)8/h2*7-9H,1-6H2,(H,11,12);1-2H,(H,5,6)(H,7,8)/b;;2-1+

SMILES Code

OC(=O)\C=C\C(O)=O.C1CC1C(NC1=NCCO1)C1CC1.C1CC1C(NC1=NCCO1)C1CC1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO and water

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO and water

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Rilmenidine binds to imidazole receptors in bovine rostral ventrolateral medulla homogenates (Ki = 6.1 nM), as well as α2-adrenergic receptors in bovine prefrontal cortex homogenates (Ki = 87 nM). Rilmenidine induces hypotension and bradycardia in anesthetized rats (ED50s = 0.25 and 0.35 mg/kg, respectively). It also reduces mean arterial pressure and renal sympathetic nerve activity in a rabbit model of renal hypertension induced by a renal artery clip when administered at a dose of 2.5 mg/kg. Rilmenidine (1 µM) increases levels of LC3-II, a marker of autophagy, in PC12 cells.

In vitro activity:

Rilmenidine modulates proliferation and stimulates the proapoptotic protein Bax, inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine renders K562 cells susceptible to doxorubicin. The rilmenidine co-treatment with doxorubicin reverses G2/M arrest and triggers apoptotic response to DNA damage. Reference: Eur J Pharm Sci. 2016 Jan 1;81:172-80. https://pubmed.ncbi.nlm.nih.gov/26598394/

In vivo activity:

This study shows that treating Caenorhabditis elegans with rilmenidine at young and older ages increases lifespan. Transcriptional changes similar to caloric restriction were observed in liver and kidney tissues in mice treated with rilmenidine. Rilmenidine has a geroprotective and potential caloric restriction mimetic effect. Reference: Aging Cell. 2023 Feb;22(2):e13774. https://pubmed.ncbi.nlm.nih.gov/36670049/

Preparing Stock Solutions

The following data is based on the product molecular weight 476.57 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Srdic-Rajic T, Nikolic K, Cavic M, Djokic I, Gemovic B, Perovic V, Veljkovic N. Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells. Eur J Pharm Sci. 2016 Jan 1;81:172-80. doi: 10.1016/j.ejps.2015.10.017. Epub 2015 Oct 24. PMID: 26598394. 2. Li F, Wu N, Su RB, Liu Y, Lu XQ, Li J. Comparison of agmatine with moxonidine and rilmenidine in morphine dependence in vitro: role of imidazoline I(1) receptors. Eur J Pharmacol. 2009 Jun 10;612(1-3):1-8. doi: 10.1016/j.ejphar.2009.03.077. Epub 2009 Apr 6. PMID: 19356733. 3. Bennett DF, Goyala A, Statzer C, Beckett CW, Tyshkovskiy A, Gladyshev VN, Ewald CY, de Magalhães JP. Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1-imidazoline receptor. Aging Cell. 2023 Feb;22(2):e13774. doi: 10.1111/acel.13774. Epub 2023 Jan 20. PMID: 36670049; PMCID: PMC9924948. 4. Underwood BR, Green-Thompson ZW, Pugh PJ, Lazic SE, Mason SL, Griffin J, Jones PS, Rowe JB, Rubinsztein DC, Barker RA. An open-label study to assess the feasibility and tolerability of rilmenidine for the treatment of Huntington's disease. J Neurol. 2017 Dec;264(12):2457-2463. doi: 10.1007/s00415-017-8647-0. Epub 2017 Oct 26. PMID: 29075837; PMCID: PMC5688221.

In vitro protocol:

In vivo protocol:

1. Bennett DF, Goyala A, Statzer C, Beckett CW, Tyshkovskiy A, Gladyshev VN, Ewald CY, de Magalhães JP. Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1-imidazoline receptor. Aging Cell. 2023 Feb;22(2):e13774. doi: 10.1111/acel.13774. Epub 2023 Jan 20. PMID: 36670049; PMCID: PMC9924948. 2. Underwood BR, Green-Thompson ZW, Pugh PJ, Lazic SE, Mason SL, Griffin J, Jones PS, Rowe JB, Rubinsztein DC, Barker RA. An open-label study to assess the feasibility and tolerability of rilmenidine for the treatment of Huntington's disease. J Neurol. 2017 Dec;264(12):2457-2463. doi: 10.1007/s00415-017-8647-0. Epub 2017 Oct 26. PMID: 29075837; PMCID: PMC5688221.

1: Perera ND, Sheean RK, Lau CL, Shin YS, Beart PM, Horne MK, Turner BJ. Rilmenidine promotes MTOR-independent autophagy in the mutant SOD1 mouse model of amyotrophic lateral sclerosis without slowing disease progression. Autophagy. 2018;14(3):534-551. doi: 10.1080/15548627.2017.1385674. Epub 2017 Dec 17. PubMed PMID: 28980850; PubMed Central PMCID: PMC5915012. 2: Rubinsztein DC, Bento CF, Deretic V. Therapeutic targeting of autophagy in neurodegenerative and infectious diseases. J Exp Med. 2015 Jun 29;212(7):979-90. doi: 10.1084/jem.20150956. Epub 2015 Jun 22. Review. PubMed PMID: 26101267; PubMed Central PMCID: PMC4493419. 3: Lim K, Jackson KL, Burke SL, Head GA. The Effects of Rilmenidine and Perindopril on Arousal Blood Pressure during 24 Hour Recordings in SHR. PLoS One. 2016 Dec 21;11(12):e0168425. doi: 10.1371/journal.pone.0168425. eCollection 2016. PubMed PMID: 28002478; PubMed Central PMCID: PMC5176293. 4: INN Common stem: -onidine. Prescrire Int. 2017 Apr;26(181):92. PubMed PMID: 30730657. 5: Mercer LD, Higgins GC, Lau CL, Lawrence AJ, Beart PM. MDMA-induced neurotoxicity of serotonin neurons involves autophagy and rilmenidine is protective against its pathobiology. Neurochem Int. 2017 May;105:80-90. doi: 10.1016/j.neuint.2017.01.010. Epub 2017 Jan 23. PubMed PMID: 28122248. 6: Kawada T, Hayama Y, Nishikawa T, Yamamoto H, Tanaka K, Sugimachi M. Even weak vasoconstriction from rilmenidine can be unmasked in vivo by opening the baroreflex feedback loop. Life Sci. 2019 Feb 15;219:144-151. doi: 10.1016/j.lfs.2019.01.009. Epub 2019 Jan 7. PubMed PMID: 30630007. 7: Underwood BR, Green-Thompson ZW, Pugh PJ, Lazic SE, Mason SL, Griffin J, Jones PS, Rowe JB, Rubinsztein DC, Barker RA. An open-label study to assess the feasibility and tolerability of rilmenidine for the treatment of Huntington's disease. J Neurol. 2017 Dec;264(12):2457-2463. doi: 10.1007/s00415-017-8647-0. Epub 2017 Oct 26. PubMed PMID: 29075837; PubMed Central PMCID: PMC5688221. 8: Montastruc JL, Macquin-Mavier I, Tran MA, Damase-Michel C, Koenig-Berard E, Valet P. Recent advances in the pharmacology of rilmenidine. Am J Med. 1989 Sep 18;87(3C):14S-17S. Review. PubMed PMID: 2571291. 9: Nascimento AR, Machado MV, Gomes F, Vieira AB, Gonçalves-de-Albuquerque CF, Lessa MA, Bousquet P, Tibiriçá E. Central Sympathetic Modulation Reverses Microvascular Alterations in a Rat Model of High-Fat Diet-Induced Metabolic Syndrome. Microcirculation. 2016 May;23(4):320-9. doi: 10.1111/micc.12280. PubMed PMID: 27086551. 10: Vucicevic J, Srdic-Rajic T, Pieroni M, Laurila JM, Perovic V, Tassini S, Azzali E, Costantino G, Glisic S, Agbaba D, Scheinin M, Nikolic K, Radi M, Veljkovic N. A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin. Bioorg Med Chem. 2016 Jul 15;24(14):3174-83. doi: 10.1016/j.bmc.2016.05.043. Epub 2016 May 24. PubMed PMID: 27265687. 11: Lewis SJ, Jarrott B, Doyle AE. Rapid eye movement (REM)-sleep during and after continuous infusion of the oxazoline derivate S3341: a comparison with clonidine. J Hypertens Suppl. 1984 Dec;2(3):S45-7. PubMed PMID: 6599698. 12: Srdic-Rajic T, Nikolic K, Cavic M, Djokic I, Gemovic B, Perovic V, Veljkovic N. Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells. Eur J Pharm Sci. 2016 Jan 1;81:172-80. doi: 10.1016/j.ejps.2015.10.017. Epub 2015 Oct 24. PubMed PMID: 26598394. 13: Nikolic K, Veljkovic N, Gemovic B, Srdic-Rajic T, Agbaba D. Imidazoline-1 receptor ligands as apoptotic agents: pharmacophore modeling and virtual docking study. Comb Chem High Throughput Screen. 2013 May;16(4):298-319. PubMed PMID: 23360165. 14: Weerasuriya K, Shaw E, Turner P. Preliminary clinical pharmacological studies of S3341, a new hypotensive agent, and comparison with clonidine in normal males. Eur J Clin Pharmacol. 1984;27(3):281-6. PubMed PMID: 6150856. 15: Mahieux F. Rilmenidine and vigilance. Review of clinical studies. Am J Med. 1989 Sep 18;87(3C):67S-72S. Review. PubMed PMID: 2571296. 16: Groenewoud G, Potgieter L, Meyer B. Bioequivalence evaluation of rilmenidine in healthy volunteers. Arzneimittelforschung. 2009;59(5):233-7. doi: 10.1055/s-0031-1296390. PubMed PMID: 19537523. 17: Genissel P, Bromet N. Pharmacokinetics of rilmenidine. Am J Med. 1989 Sep 18;87(3C):18S-23S. PubMed PMID: 2782323. 18: Dresse A, Scuvée-Moreau J. Influence of the alpha-2 agonist oxaminozoline (S3341) on firing rate of central noradrenergic and serotonergic neurons in the rat. Comparison with clonidine. Arch Int Physiol Biochim. 1986 Jun;94(2):99-106. PubMed PMID: 2430542. 19: Lewis SJ, Jarrott B, Doyle AE. Rapid eye movement sleep and the associated cardiovascular changes during and after continuous 10-day infusion of clonidine in normotensive rats: comparison with lofexidine and S3341. J Cardiovasc Pharmacol. 1987 Jun;9(6):711-8. PubMed PMID: 2442539. 20: Montastruc JL, Macquin-Mavier I, Damase-Michel C, Dard B, Tran MA, Valet P. [Current data on the pharmacology of rilmenidine]. Arch Mal Coeur Vaiss. 1989 Dec;82 Spec No 5:25-9. Review. French. PubMed PMID: 2517006.