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]
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]
Stimulants: Phenylethanolamine
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