Erythrohydrobupropion (developmental codes 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 a racemic mixture of two stereoisomers, (1R,2S)-erythrohydrobupropion and (1S,2R)-erythrohydrobupropion.[3][1] Other metabolites of bupropion include hydroxybupropion and threohydrobupropion.[1][2]
 (1S,2R)-Erythrohydrobupropion | |
| Clinical data | |
|---|---|
| Other names | erythro-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 | |
| Metabolism | Hydroxylation (CYP2B6, CYP2C19), glucuronidation (UGTs)[1] |
| Elimination half-life | 33 hours[1] |
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| Chemical and physical data | |
| Formula | C13H20ClNO |
| Molar mass | 241.76 g·mol−1 |
| 3D model (JSmol) | |
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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
edit- ^ a b c d e f g h i j k l m n o p q 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 163167323.293-313&rft.date=2019-08&rft_id=https://api.semanticscholar.org/CorpusID:163167323#id-name=S2CID&rft_id=info:pmid/31124380&rft_id=info:doi/10.1080/03602532.2019.1620763&rft.aulast=Costa&rft.aufirst=R&rft.au=Oliveira, NG&rft.au=Dinis-Oliveira, RJ&rfr_id=info:sid/en.wikipedia.org:Erythrohydrobupropion" class="Z3988">
- ^ a b c d e f g h 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 16368442.1685-95&rft.date=2005-11&rft_id=info:doi/10.1016/j.clinthera.2005.11.011&rft_id=info:pmid/16368442&rft.aulast=Jefferson&rft.aufirst=JW&rft.au=Pradko, JF&rft.au=Muir, KT&rfr_id=info:sid/en.wikipedia.org:Erythrohydrobupropion" class="Z3988">
- ^ 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 27255113.230-8&rft.date=2016-08&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959100#id-name=PMC&rft_id=info:pmid/27255113&rft_id=info:doi/10.1124/jpet.116.232876&rft.aulast=Masters&rft.aufirst=AR&rft.au=Gufford, BT&rft.au=Lu, JB&rft.au=Metzger, IF&rft.au=Jones, DR&rft.au=Desta, Z&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959100&rfr_id=info:sid/en.wikipedia.org:Erythrohydrobupropion" class="Z3988">