Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIT4QCDBF)
  Drug Name Amphetamine Drug Info Guanethidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Cns Stimulants Antihypertensive Agents
  Structure

 Mechanism of Amphetamine-Guanethidine Interaction (Severity Level: Moderate)
     Antagonize the effect of antihypertensive agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Amphetamine Guanethidine
      Mechanism Hypertensive effects Hypotensive effects
Synaptic vesicular amine transporter  Inhibitor
      Key Mechanism Factor 1
Factor Name Synaptic vesicle amine transporter
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Structure Sequence
MALSELALVRWLQESRRSRKLILFIVFLALLLDNMLLTVVVPIIPSYLYSIKHEKNATEIQTARPVHTASISDSFQSIFSYYDNSTMVTGNATRDLTLHQTATQHMVTNASAVPSDCPSEDKDLLNENVQVGLLFASKATVQLITNPFIGLLTNRIGYPIPIFAGFCIMFVSTIMFAFSSSYAFLLIARSLQGIGSSCSSVAGMGMLASVYTDDEERGNVMGIALGGLAMGVLVGPPFGSVLYEFVGKTAPFLVLAALVLLDGAIQLFVLQPSRVQPESQKGTPLTTLLKDPYILIAAGSICFANMGIAMLEPALPIWMMETMCSRKWQLGVAFLPASISYLIGTNIFGILAHKMGRWLCALLGMIIVGVSILCIPFAKNIYGLIAPNFGVGFAIGMVDSSMMPIMGYLVDLRHVSVYGSVYAIADVAFCMGYAIGPSAGGAIAKAIGFPWLMTIIGIIDILFAPLCFFLRSPPAKEEKMAILMDHNCPIKTKMYTQNNIQSYPIGEDEESESD
Gene Name SLC18A2
Uniprot ID VMAT2_HUMAN
KEGG Pathway hsa:6571
Protein Family Major facilitator superfamily
Protein Function
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles (PubMed:23363473). Requisite for vesicular amine storage prior to secretion via exocytosis.
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      Mechanism Description
  • Antagonize the effect of Amphetamine when combined with Guanethidine 

Recommended Action
      Management alternatives to postganglionic adrenergic blocking agents should be considered in hypertensive patients treated with CNS stimulants. If the combination is used, blood pressure and heart rate should be monitored.

References
1 Gulati OD, Dave BT, Gokhale SD, Shah KM "Antagonism of adrenergic neuron blockade in hypertensive subjects." Clin Pharmacol Ther 7 (1966): 510-4. [PMID: 5939974]
2 Gerkens JF, McCulloch MW, Wilson J "Mechanism of the antagonism between guanethidine and dexamphetamine." Br J Pharmacol 35 (1969): 563-72
3 Flegin OT, Morgan DH, Oates JA, Shand DG, Turner P "The mechanism of the reversal of the effect of guanethidine by amphetamines in cat and man." Br J Pharmacol 39 (1970): p253