Erythrohydrobupropion

Erythrohydrobupropion (developmental code names BW 287, BW 17U) is a substituted amphetamine derivative—specifically a β-hydroxyamphetamine—and a minor active metabolite of the antidepressant drug bupropion (Wellbutrin).[1][2] Bupropion is a norepinephrine–dopamine reuptake inhibitor and nicotinic acetylcholine receptor negative allosteric modulator, with its metabolites contributing substantially to its activities.[1] Erythrohydrobupropion exists as two isomers, (1R,2S)-erythrohydrobupropion and (1S,2R)-erythrohydrobupropion.[3][1] Other metabolites of bupropion include hydroxybupropion and threohydrobupropion.[1][2]

Erythrohydrobupropion
Clinical data
Other nameserythro-Hydrobupropion; Erythrohydroxybupropion; BW 287; BW 17U; erythro-3-Chloro-N-tert-butyl-β-hydroxy-α-methylphenethylamine; erythro-3-Chloro-N-tert-butyl-β-hydroxyamphetamine
Pharmacokinetic data
MetabolismHydroxylation (CYP2B6, CYP2C19), glucuronidation (UGTs)[1]
Elimination half-life33 hours[1]
Identifiers
  • 2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-ol
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC13H20ClNO
Molar mass241.76 g·mol−1
3D model (JSmol)
  • CC(C(C1=CC(=CC=C1)Cl)O)NC(C)(C)C
  • InChI=1S/C13H20ClNO/c1-9(15-13(2,3)4)12(16)10-6-5-7-11(14)8-10/h5-9,12,15-16H,1-4H3
  • Key:NDPTTXIBLSWNSF-UHFFFAOYSA-N

Information on the pharmacological actions of erythrohydrobupropion is scarce.[1] 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.[1][2] It circulates at similar concentrations as bupropion during bupropion therapy.[1][2] Conversely, two other metabolites, hydroxybupropion and threohydrobupropion, circulate at higher concentrations than bupropion.[1][2]

Erythrohydrobupropion is formed from bupropion via reduction of the ketone group primarily by 11β-hydroxysteroid dehydrogenase-1 and to a minor extent by aldo-keto reductases.[1] It can also be formed from bupropion by carbonyl reductases.[1][2] The compound is metabolized by the cytochrome P450 enzymes CYP2B6 and CYP2C19 into erythro-4'-hydroxy-hydrobupropion and by various glucuronosyltransferase enzymes into glucuronide conjugates.[1] The elimination half-life of erythrohydrobupropion is approximately 33 hours.[1][2] Its half-life may be longer in older people.[2]

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

References
  1. Costa R, Oliveira NG, Dinis-Oliveira RJ (August 2019). "Pharmacokinetic and pharmacodynamic of bupropion: integrative overview of relevant clinical and forensic aspects". Drug Metab Rev. 51 (3): 293–313. doi:10.1080/03602532.2019.1620763. PMID 31124380. S2CID 163167323.
  2. Jefferson JW, Pradko JF, Muir KT (November 2005). "Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations". Clin Ther. 27 (11): 1685–95. doi:10.1016/j.clinthera.2005.11.011. PMID 16368442.
  3. Masters AR, Gufford BT, Lu JB, Metzger IF, Jones DR, Desta Z (August 2016). "Chiral Plasma Pharmacokinetics and Urinary Excretion of Bupropion and Metabolites in Healthy Volunteers". J Pharmacol Exp Ther. 358 (2): 230–8. doi:10.1124/jpet.116.232876. PMC 4959100. PMID 27255113.


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