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rilmenidine

Indications: - treatment of hypertension Contraindications: - severe depression - chronic renal failure stage 5 (eGFR < 15 mL/min) [3] - avoid in pregnant women & in lactation* * no teratogenic or embryotoxic effects have been observed in animal studies * rilmenidine is excreted in breast milk Dosage: 1-2 mg QD in morning tablets: 1 mg - do not discontinue abruptly, reduce dosage gradually Dosage adjustment in renal failure: - none if eGFR > 15 mL/min Adverse effects: - rare, non-severe, & transient at therapeutic doses: - asthenia, palpitations, insomnia, drowsiness, fatigue on exercise, epigastric pain, dry mouth, diarrhea, skin rash - cold extremities, postural hypotension, sexual disorders, anxiety, depression, pruritus, edema, cramps, nausea, constipation, hot flushes - 2 mg dose of rilmenidine with fewer & less severe adverse effects vs clonidine (0.15-0.30 mg/day) or alpha-methyldopa (500-1000 mg/day) * overdose: - no cases of massive overdose reported - hypotension & drowsiness anticipated - gastric lavage recommended - sympathomimetics may be required - rilmenidine is only slightly dialysable Drug interactions: - combination with MAOIs is not recommended - caution when used in combination with tricyclic antidepressants - avoid in combination with alcohol Mechanism of action: - nischarin agonist - activation of nischarin by rilmenidine increases phosphorylation of mitogen-activated protein kinases MAPK1 & MAPK3 in rostral ventrolateral medulla neurons that exhibit rilmenidine-evoked hypotension - also effects peripheral vasomotor structures - greater selectivity for imidazoline receptors than for cerebral alpha2-adrenergic receptors - anti-inflammatory properties Comparative biology: - rilmenidine extends lifespan of C elegans - rilmenidine-induced longevity requires transcription factors FOXO/DAF-16 & NRF1,2,3/SKN-1 - autophagy signaling is also needed for rilmenidine-induced longevity - AMPK signaling plays no significant role in longevity

Interactions

drug adverse effects of antihypertensive agents

General

antihypertensive agent

Database Correlations

PUBCHEM cid=68712

References

  1. Reid JL. Rilmenidine: a clinical overview. Am J Hypertens. 2000 Jun;13(6 Pt 2):106S-111S. PMID: 10921529 Review. - Reid JL. Update on rilmenidine: clinical benefits. Am J Hypertens. 2001 Nov;14(11 Pt 2):322S-324S. PMID: 11721891 Review.
  2. Bennett DF, Goyala A, Statzer C et al Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1-imidazoline receptor. Aging Cell. 2023 Feb;22(2):e13774. PMID: 36670049 PMCID: PMC9924948 Free PMC article
  3. Wikipedia: Rilmenidine https://en.wikipedia.org/wiki/Rilmenidine