Drug General Information (ID: DDI1G3DOIZ)
  Drug Name Venlafaxine Drug Info Clonidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antihypertensive Agents
  Structure

 Mechanism of Venlafaxine-Clonidine Interaction (Severity Level: Moderate)
     Additive CNS depression effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Venlafaxine Clonidine
      Mechanism 1 CNS depression effects CNS depression effects
      Key Mechanism Factor 1
Factor Name CNS depression effects
Factor Description CNS depressants are drugs that inhibit or suppress brain activity and can reduce mental and physical processes. Excessive CNS depression can lead to decreased heart rate, slow breathing (less than 10 breaths per minute), extreme confusion or loss of memory, nausea and vomiting, poor judgment, blue lips or fingertips, irritability and aggression, and clammy or cold skin.
      Mechanism Description
  • Additive CNS depression effects by the combination of Venlafaxine and Clonidine 
     Antagonize the effect of antihypertensive agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Venlafaxine Clonidine
      Mechanism 2 Hypertensive effects
Alpha-2 adrenergic receptor  Antagonist
Antihypertensive agent
Alpha-2 adrenergic receptor  Agonist
      Key Mechanism Factor 2
Factor Name Adrenergic receptor alpha-2 Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
    Click to Show/Hide
      Mechanism Description
  • Antagonize the effect of Venlafaxine when combined with Clonidine 

Recommended Action
      Management If concomitant use cannot be avoided, monitoring for altered efficacy of clonidine is recommended. In some cases, the dosage of clonidine may require upward adjustment.

References
1 Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):.
2 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
3 Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.