Threohydrobupropion

Overview

Threohydrobupropion (developmental code names BW 494, BW A494U) is a substituted amphetamine derivative—specifically a β-hydroxyamphetamine—and a major active metabolite of the antidepressant drug bupropion (Wellbutrin). Bupropion is a norepinephrine–dopamine reuptake inhibitor and nicotinic acetylcholine receptor negative allosteric modulator, with its metabolites contributing substantially to its activities.[1][2] WP

Pharmacology

Pharmacology

Information on the pharmacological actions of threohydrobupropion is scarce. In any case, it is about 20% as pharmacologically potent as bupropion and in the range of 20 to 50% as potent as bupropion in mouse models of depression. Moreover, threohydrobupropion has been reported to weakly inhibit the reuptake of norepinephrine, dopamine, and serotonin with rat IC₅₀ (half-maximal inhibitory concentration) or Kᵢ values of 16 μM, 47 μM, and 67 μM, respectively. These values can be compared to rat values with bupropion of 1,400 nM, 570 nM, and 19,000 nM, respectively. Besides monoamine reuptake inhibition, threohydrobupropion has also been reported to inhibit α₃β₄ nicotinic acetylcholine receptors, with an IC₅₀ value of 14 μM. Threohydrobupropion circulates at higher concentrations than bupropion during bupropion therapy, similarly to hydroxybupropion but in contrast to erythrohydrobupropion—which circulates at similar concentrations as bupropion.[1–4] WP

The plasma protein binding of threohydrobupropion is 42%. Threohydrobupropion is formed from bupropion via reduction of the ketone group by 11β-hydroxysteroid dehydrogenase-1 and aldo-keto reductases. It can also be formed from bupropion by carbonyl reductases. The compound is metabolized by the cytochrome P450 enzymes CYP2B6 and CYP2C19 into threo-4'-hydroxy-hydrobupropion and by various glucuronosyltransferase enzymes into glucuronide conjugates. Its elimination half-life is approximately 37 hours.[1][2] WP

Dry mouth during bupropion therapy has been associated with threohydrobupropion concentrations. Administration of threohydrobupropion in mice produces seizures at sufficiently high doses similarly to bupropion and other metabolites. Threohydrobupropion is a CYP2D6 inhibitor and accounts for about 21% of CYP2D6 inhibition during bupropion therapy, with hydroxybupropion accounting for 65% and erythrohydrobupropion accounting for 9%.[1] WP

Chemistry

Formula

C13H20ClNO PC

Molar mass (g/mol)

241.76 PC

IUPAC name (computed by PubChem)

(1R,2R)-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-ol PC

SMILES

C[C@H]([C@@H](C1=CC(=CC=C1)Cl)O)NC(C)(C)C PC

InChIKey

NDPTTXIBLSWNSF-SKDRFNHKSA-N PC

PubChem CID

9943534

IUPAC name

rel-(1R*,2R*)-2-(tert-Butylamino)-1-(3-chlorophenyl)propan-1-ol WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

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Sources

1. Journal / agency Costa R, Oliveira NG, Dinis-Oliveira RJ. Pharmacokinetic and pharmacodynamic of bupropion: integrative overview of relevant clinical and forensic aspects. Drug Metab Rev. August 2019. doi:10.1080/03602532.2019.1620763 · PMID 31124380
2. Journal / agency Jefferson JW, Pradko JF, Muir KT. Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations. Clin Ther. November 2005. doi:10.1016/j.clinthera.2005.11.011 · PMID 16368442
3. Journal / agency Sánchez C, Hyttel J. Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. Cell Mol Neurobiol. August 1999. doi:10.1023/a:1006986824213 · PMID 10379421 · PMC11545528
4. Journal / agency Bondarev ML, Bondareva TS, Young R, Glennon RA. Behavioral and biochemical investigations of bupropion metabolites. Eur J Pharmacol. August 2003. doi:10.1016/s0014-2999(03)02010-7 · PMID 12909199

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.