rilmenidine

Indications

• treatment of hypertension

Contraindications

• severe depression
• chronic renal failure stage 5 (eGFR < 15 mL/min)
• 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 adverse effects of antihypertensive agents

Drug interactions

• combination with MAOIs is not recommended
• caution when used in combination with tricyclic antidepressants
• avoid in combination with alcohol

• drug interaction(s) of NSAIDs & antihypertensives

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

More general terms

• antihypertensive agent

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=68712