Rilmenidine

Rilmenidine

Clinical data
Trade names	Albarel
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	C02AC06 ( WHO )
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding	7%
Metabolism	Minimal
Elimination half-life	8 hours
Excretion	Renal, unchanged
Identifiers
IUPAC name N-(dicyclopropylmethyl)-4,5-dihydro-1,3-oxazol-2-amine
CAS Number	54187-04-1  N
PubChem CID	68712
ChemSpider	61963  Y
UNII	P67IM25ID8
ChEMBL	ChEMBL289480  Y
CompTox Dashboard (EPA)	DTXSID3045194
ECHA InfoCard	100.053.638
Chemical and physical data
Formula	C10H16N2O
Molar mass	180.251 g·mol−1
3D model (JSmol)	Interactive image
SMILES O1CCN=C1NC(C2CC2)C3CC3
InChI 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) Y Key:CQXADFVORZEARL-UHFFFAOYSA-N Y
NY  (what is this?)    (verify)

Rilmenidine is a prescription medication for the treatment of hypertension. ^[1] It is taken orally and marketed under the brand names Albarel, Hyperium, Iterium and Tenaxum.

Mechanism of action

Rilmenidine, an oxazoline compound with antihypertensive properties, acts on both medullary and peripheral vasomotor structures.

Rilmenidine is a imidazoline analog and shows greater selectivity for imidazoline receptors than for cerebral alpha2-adrenergic receptors, distinguishing it from reference alpha2-agonists, and conferring additional anti-inflammatory actions not shared with most other antihypertensive drugs. ^{[2] [3] [4] [5]}

Contraindications

Severe depression, severe kidney failure (creatinine clearance <15 ml/min), as a precaution in the absence of currently available studies.

Dosage and route of administration

The recommended dosage is 1 tablet per day as a single morning administration. (Each tablet contains 1.544 mg rilmenidine dihydrogen phosphate, an amount equivalent to 1 mg of rilmenidine base.) If results are not adequate after 1 month of treatment, the dosage may be increased to 2 tablets per day, given in divided doses (1 tablet morning and evening) before meals. As a result of its good clinical and biological acceptability, rilmenidine may be administered to both elderly and diabetic hypertensive patients. In patients with kidney failure, no dosage adjustment is necessary in principle when the creatinine clearance is greater than 15 mL/min.

Treatment may be continued indefinitely.

Precautions

• As with all antihypertensive agents, regular medical monitoring is required when rilmenidine is administered to patients with a recent history of cardiovascular disease (stroke, myocardial infarction).
• Alcohol consumption should be avoided during treatment.
• In patients with kidney failure, no dosage adjustment is necessary if creatinine clearance is greater than 15 mL/min.
• In the absence of documented experiments in this area, rilmenidine is not recommended for prescription to children.
• Pregnancy: as with all new molecules, administration of rilmenidine should be avoided in pregnant women, although no teratogenic or embryotoxic effects have been observed in animal studies.
• Lactation: rilmenidine is excreted in breast milk, and its use is therefore not recommended during lactation.
• Effects on the ability to drive motor vehicles or operate machinery: double-blind, placebo-controlled studies have not shown rilmenidine to have any effect on alertness at therapeutic doses (1 or 2 daily administrations of 1 mg). If these doses are exceeded, or if rilmenidine is combined with other drugs capable of reducing alertness, vehicle drivers or machine operators should be warned of the possibility of drowsiness.

Drug interactions

Combination with MAOIs is not recommended; combination with tricyclic antidepressants requires prudence, as the antihypertensive activity of rilmenidine may be partly antagonized.

Side effects

• At a dose of 1 mg given as a single daily administration during controlled trials, the incidence of side effects was comparable to that observed with placebo.
• At a dose of 2 mg per day of rilmenidine, controlled comparative studies versus clonidine (0.15 to 0.30 mg/day) or alpha-methyldopa (500 to 1000 mg/day) demonstrated that the incidence of side effects was significantly lower with rilmenidine than with either clonidine or a-methyldopa.

Side-effects are rare, non-severe, and transient at therapeutic doses: asthenia, palpitations, insomnia, drowsiness, fatigue on exercise, epigastric pain, dryness of the mouth, diarrhea, skin rash; and exceptionally, cold extremities, postural hypotension, sexual disorders, anxiety, depression, pruritus, edema, cramps, nausea, constipation, hot flushes.

Overdosage

No cases of massive absorption have been reported. Likely symptoms in such an eventuality would be marked hypotension and lowered alertness. In addition to gastric lavage, sympathomimetic agents may also be required. Rilmenidine is only slightly dialysable.

Research

The drug has been shown to mimic the lifespan-extending effects of calorie restriction in cell cultures and in the worm C. elegans. ^[6]

See also

• Moxonidine

References

1. Remková A, Kratochvíl'ová H (August 2002). "Effect of the new centrally acting antihypertensive agent rilmenidine on endothelial and platelet function in essential hypertension". Journal of Human Hypertension. 16 (8): 549–55. doi: 10.1038/sj.jhh.1001427 . PMID   12149660.
2. Cobos-Puc L, Aguayo-Morales H (2019). "Cardiovascular Effects Mediated by Imidazoline Drugs: An Update". Cardiovascular & Hematological Disorders Drug Targets. 19 (2): 95–108. doi:10.2174/1871529X18666180629170336. PMID   29962350. S2CID   49644599.
3. Bousquet P, Hudson A, García-Sevilla JA, Li JX (January 2020). "Imidazoline Receptor System: The Past, the Present, and the Future". Pharmacological Reviews. 72 (1): 50–79. doi: 10.1124/pr.118.016311 . PMID   31819014.
4. Bennett DF, Goyala A, Statzer C, Beckett CW, Tyshkovskiy A, Gladyshev VN, et al. (February 2023). "Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1-imidazoline receptor". Aging Cell. 22 (2): e13774. doi:10.1111/acel.13774. PMC   9924948 . PMID   36670049.
5. Yalçın MB, Bora ES, Çakır A, Akbulut S, Erbaş O (2023). "Autophagy and anti-inflammation ameliorate diabetic neuropathy with Rilmenidine". Acta Cirurgica Brasileira. 38: e387823. doi:10.1590/acb387823. PMC   10691181 . PMID   38055406.
6. Nield, David (2024-08-27). "Common Blood Pressure Drug Extends Lifespan And Slows Aging in Animals". ScienceAlert. Retrieved 2024-09-11.