Drug General Information (ID: DDIRIBA6VQ)
  Drug Name Cariprazine Drug Info Levomilnacipran Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Atypical Antipsychotics Snris/Antidepressants
  Structure

 Mechanism of Cariprazine-Levomilnacipran Interaction (Severity Level: Moderate)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Cariprazine Levomilnacipran
      Mechanism Serotonergic effects Serotonergic effects
Serotonin transporter  Inhibitor
      Key Mechanism Factor 1
Factor Name Serotonin transporter
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Structure Sequence
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTRHSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLPYTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIMAWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIHRSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGATLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQDALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPASTFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVTLTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRICWVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIITPGTFKERIIKSITPETPTEIPCGDIRLNAV
Gene Name SLC6A4
Uniprot ID SC6A4_HUMAN
KEGG Pathway hsa:6532
Protein Family Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
Protein Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
    Click to Show/Hide
      Mechanism Description
  • Additive serotonergic effects by the combination of Cariprazine and Levomilnacipran 

Recommended Action
      Management Caution is advised if milnacipran or levomilnacipran is prescribed in combination with neuroleptic agents. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures. Patients receiving milnacipran or levomilnacipran with neuroleptic agents should be apprised of potentially additive CNS effects and avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them.

References
1 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
2 Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.
3 Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]