Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIODC9KN0)
  Drug Name Milrinone Drug Info Nefazodone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Cardiotonic Agents Antidepressants
  Structure

 Mechanism of Milrinone-Nefazodone Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Milrinone Nefazodone
      Mechanism Hypotensive effects
Phosphodiesterase 3  Inhibitor 		Potentiate the hypotensive effect of antihypertensive agents
      Key Mechanism Factor 1
Factor Name Phosphodiesterase 3 Structure Sequence
Protein Family Cyclic nucleotide phosphodiesterase family
Protein Function
Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:8695850, PubMed:8155697, PubMed:25961942). Has also activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099).
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Milrinone and Nefazodone 

Recommended Action
      Management Caution and close monitoring for altered efficacy and safety are recommended if patients receive nefazodone with agents that can produce significant hypotension such as antihypertensive agents or vasodilators. Patients should be made aware of the possible side effects (e.g., dizziness, lightheadedness, orthostasis) and be cautioned about driving, operating machinery, or performing other hazardous tasks.

References
1 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
2 Product Information. Serzone (nefazodone). Bristol-Myers Squibb, Princeton, NJ.
3 Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]