PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs. Cytochrome P450 enzymes - 2A6.

PsychoTropicalResearch, serotonin and serotonin syndrome research.

Cytochrome P450 enzymes - 2A6

Cytochrome P450 enzymes - 2A6

Inhibitors

potent and selective

  • Methoxsalen (8-methoxypsoralen)
  • Tranylcypromine
  • Dialkyl disulfides [di-n-propyl disulfide, contained in onion oil- the most potent]
  • Diallyl disulfide, present in garlic oil [K(i) value of 2.13 microM].

Substrates

  • Dexmedetomidine (Alpha 2 agonist- sedative)
  • nicotine (urinary cotinine, one of the main metabolites of nicotine, has been widely used as a biomarker for assessment of direct or passive exposure to cigarette smoke)
  • 1,7-dimethylxanthine (marker, caffeine metabolite)

coumarin 7-hydroxylation

CYP2A6 activates tobacco smoke pro-carcinogens (nitrosamines)

Conversion of the caffeine metabolite 1,7-dimethylxanthine (17X) to 1,7-dimethyl uric acid (17U) is catalyzed primarily by CYP2A6

Inhibiting CYP2A6 in vivo decreased nicotine metabolism and smoking behavior.
activation of tobacco nitrosamines.

CYP2A6 genetic polymorphisms may influence tobacco dependence and consumption.

Halothane causes lipid peroxidation in human liver microsomes, which is catalyzed by CYP2A6