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 | |
| Clinical data | |
|---|---|
| Other names | threo-Hydrobupropion; Threohydroxybupropion; BW 494; BW A494U; threo-3-Chloro-N-tert-butyl-β-hydroxy-α-methylphenethylamine; threo-3-Chloro-N-tert-butyl-β-hydroxyamphetamine |
| Pharmacokinetic data | |
| Protein binding | 42% [1] |
| Metabolism | Hydroxylation ( CYP2B6, CYP2C19), glucuronidation ( UGTs) [1] |
| Elimination half-life | 37 hours [1] [2] |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| ChEMBL | |
| CompTox Dashboard ( EPA) | |
| ECHA InfoCard | 100.216.731 |
| Chemical and physical data | |
| Formula | C13H20ClNO |
| Molar mass | 241.76 g·mol−1 |
| 3D model ( JSmol) | |
| |
| |
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). [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] Threohydrobupropion exists as two isomers, (1R,2R)-threohydrobupropion and (1S,2S)-threohydrobupropion. [3] [1] Other metabolites of bupropion include hydroxybupropion and erythrohydrobupropion. [1] [2]
Information on the pharmacological actions of threohydrobupropion 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] Moreover, threohydrobupropion has been reported to weakly inhibit the reuptake of norepinephrine, dopamine, and serotonin with rat IC50 or Ki values of 16 μM, 47 μM, and 67 μM, respectively. [4] These values can be compared to rat values with bupropion of 1,400 nM, 570 nM, and 19,000 nM, respectively. [4] Besides monoamine reuptake inhibition, threohydrobupropion has also been reported to inhibit α3β4 nicotinic acetylcholine receptors, with an IC50 value of 14 μM. [5] 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] [2]
The plasma protein binding of threohydrobupropion is 42%. [1] Threohydrobupropion is formed from bupropion via reduction of the ketone group by 11β-hydroxysteroid dehydrogenase-1 and 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 threo-4'-hydroxy-hydrobupropion and by various glucuronosyltransferase enzymes into glucuronide conjugates. [1] Its elimination half-life is approximately 37 hours. [1] [2]
Dry mouth during bupropion therapy has been associated with threohydrobupropion concentrations. [1] Administration of threohydrobupropion in mice produces seizures at sufficiently high doses similarly to bupropion and other metabolites. [1] 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]
References
- ^ a b c d e f g h i j k l m n o p q r 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.
- ^ a b c d e f g 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.
- ^ 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.
- ^ a b Sánchez C, Hyttel J (August 1999). "Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding". Cell Mol Neurobiol. 19 (4): 467–89. doi: 10.1023/a:1006986824213. PMID 10379421. S2CID 19490821.
- ^ Bondarev ML, Bondareva TS, Young R, Glennon RA (August 2003). "Behavioral and biochemical investigations of bupropion metabolites". Eur J Pharmacol. 474 (1): 85–93. doi: 10.1016/s0014-2999(03)02010-7. PMID 12909199.
 | This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it. |
| This article has multiple issues. Please help
improve it or discuss these issues on the
talk page. (
Learn how and when to remove these template messages)
|
|
| |
| Clinical data | |
|---|---|
| Other names | threo-Hydrobupropion; Threohydroxybupropion; BW 494; BW A494U; threo-3-Chloro-N-tert-butyl-β-hydroxy-α-methylphenethylamine; threo-3-Chloro-N-tert-butyl-β-hydroxyamphetamine |
| Pharmacokinetic data | |
| Protein binding | 42% [1] |
| Metabolism | Hydroxylation ( CYP2B6, CYP2C19), glucuronidation ( UGTs) [1] |
| Elimination half-life | 37 hours [1] [2] |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| ChEMBL | |
| CompTox Dashboard ( EPA) | |
| ECHA InfoCard | 100.216.731 |
| Chemical and physical data | |
| Formula | C13H20ClNO |
| Molar mass | 241.76 g·mol−1 |
| 3D model ( JSmol) | |
| |
| |
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). [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] Threohydrobupropion exists as two isomers, (1R,2R)-threohydrobupropion and (1S,2S)-threohydrobupropion. [3] [1] Other metabolites of bupropion include hydroxybupropion and erythrohydrobupropion. [1] [2]
Information on the pharmacological actions of threohydrobupropion 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] Moreover, threohydrobupropion has been reported to weakly inhibit the reuptake of norepinephrine, dopamine, and serotonin with rat IC50 or Ki values of 16 μM, 47 μM, and 67 μM, respectively. [4] These values can be compared to rat values with bupropion of 1,400 nM, 570 nM, and 19,000 nM, respectively. [4] Besides monoamine reuptake inhibition, threohydrobupropion has also been reported to inhibit α3β4 nicotinic acetylcholine receptors, with an IC50 value of 14 μM. [5] 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] [2]
The plasma protein binding of threohydrobupropion is 42%. [1] Threohydrobupropion is formed from bupropion via reduction of the ketone group by 11β-hydroxysteroid dehydrogenase-1 and 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 threo-4'-hydroxy-hydrobupropion and by various glucuronosyltransferase enzymes into glucuronide conjugates. [1] Its elimination half-life is approximately 37 hours. [1] [2]
Dry mouth during bupropion therapy has been associated with threohydrobupropion concentrations. [1] Administration of threohydrobupropion in mice produces seizures at sufficiently high doses similarly to bupropion and other metabolites. [1] 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]
References
- ^ a b c d e f g h i j k l m n o p q r 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.
- ^ a b c d e f g 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.
- ^ 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.
- ^ a b Sánchez C, Hyttel J (August 1999). "Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding". Cell Mol Neurobiol. 19 (4): 467–89. doi: 10.1023/a:1006986824213. PMID 10379421. S2CID 19490821.
- ^ Bondarev ML, Bondareva TS, Young R, Glennon RA (August 2003). "Behavioral and biochemical investigations of bupropion metabolites". Eur J Pharmacol. 474 (1): 85–93. doi: 10.1016/s0014-2999(03)02010-7. PMID 12909199.
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| This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it. |