What is the mechanism of action of bupropion?
Preclinical and clinical data demonstrate that bupropion acts via dual inhibition of norepinephrine and dopamine reuptake, which constitutes a novel mechanism of antidepressant action. As such, bupropion is associated with a unique clinical profile with efficacy comparable to that of other antidepressants.
Is bupropion a CYP inhibitor?
Bupropion is therefore a potent inhibitor of CYP2D6 activity, and care should be exercised when initiating or discontinuing bupropion use in patients taking drugs metabolized by CYP2D6.
What is bupropion metabolized by?
Bupropion and its metabolites Bupropion is metabolized by both CYP2B6 and CR to form hydroxybupropion and threo/erythrohydrobupropion, respectively 8, 9, 10. It is also known that threo/erythrohydrobupropion can further undergo glucuronidation 20.
What CYP metabolizes bupropion?
CYP2B6
Bupropion is metabolized by CYP2B6 to form hydroxybupropion and by carbonyl reductase to form the diastereoisomers threohydrobupropion and erythrohydrobupropion.
What receptors does bupropion work?
A more recently discovered pharmacological property of bupropion is its affinity for nicotinic receptors. Bupropion is a non-competitive antagonist of nicotinic acetylcholine receptors. This is thought to contribute to its antidepressant effects, as well as to its effectiveness as a smoking cessation drug.
Does bupropion block acetylcholine?
In addition, bupropion blocks nicotine activation of alpha(3)beta(2), alpha(4)beta(2), and alpha(7) neuronal acetylcholine nicotinic receptors (nAChRs) with some degree of selectivity. It was approximately 50 and 12 times more effective in blocking alpha(3)beta(2) and alpha(4)beta(2) than alpha(7.)
Where is Wellbutrin metabolized?
Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys.
Does bupropion inhibit CYP3A4?
A study in human liver microsomes suggests that CYP3A4 does not significantly catalyze bupropion hydroxylation [Article:11454731]. The amino-alcohol isomers threohydrobupropion and erythrohydrobupropion are other metabolites of bupropion, which are formed via reduction of the carbonyl group [Article:18420781].
What enzymes metabolizes Wellbutrin?
enzyme CYP2B6
Since bupropion is metabolized to hydroxybupropion by the enzyme CYP2B6, drug interactions with CYP2B6 inhibitors are possible: this includes such medications as paroxetine, sertraline, norfluoxetine (active metabolite of fluoxetine), diazepam, clopidogrel, and orphenadrine.
Where does Wellbutrin metabolize?
Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and subsequently excreted by the kidneys.
Is Wellbutrin an inducer or inhibitor?
Bupropion (also known as the brand name product Wellbutrin®) is a norepinephrine/dopamine-reuptake inhibitor (NDRI) used most commonly for the management of Major Depressive Disorder (MDD), Seasonal Affective Disorder (SAD), and as an aid for smoking cessation.
What neurotransmitter does bupropion effect?
Bupropion inhibits the presynaptic reuptake of both dopamine (DA) and noradrenaline (NA), leading to increased levels of both of these neurotransmitters in the synaptic cleft (Figure 23-6).
What is cytochromes P450?
S.J. Charnock, in Advances in Protein Chemistry and Structural Biology, 2016. Cytochromes P450, a family of heme-containing monooxygenases that catalyze a diverse range of oxidative reactions, are so-called due to their maximum absorbance at 450 nm, ie, “Pigment–450 nm,” when bound to carbon monoxide.
What is the oxygen rebound mechanism of cytochrome P450?
Oxygen rebound mechanism utilized by cytochrome P450 for conversion of hydrocarbons to alcohols via the action of “compound I”, an iron (IV) oxide bound to a heme radical cation. An alternative route for mono-oxygenation is via the “peroxide shunt” (path “S” in figure).
What is the meaning of P450?
The term “P450” is derived from the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme (450 nm) when it is in the reduced state and complexed with carbon monoxide. Most CYPs require a protein partner to deliver one or more electrons to reduce the iron (and eventually molecular oxygen).