Synthesis and evaluation of the antidepressant activity of the enantiomers of bupropion

Musso, David L.; Mehta, Nariman B.; Soroko, Francis E.; Ferris, Robert M.; Hollingsworth, Elizabeth B.; Kenney, Bernard T.

doi:10.1002/chir.530050704

Cited by 39 publications

(24 citation statements)

References 5 publications

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“…For example, similar to tricyclics and monoamine oxidase inhibitors, bupropion reverses sedation and ptosis induced by tetrabenazine (2,118) and hypothermia induced by reserpine (106). Furthermore, bupropion has been shown to reduce immobility in the behavioral despair (16,106) and tail-suspension (144) tests, and to attenuate behavioral deficits in a chronic-stress paradigm (89).…”

Section: Animal Models Of Depressionmentioning

confidence: 99%

Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent

et al. 2006

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Bupropion hydrochloride ((±)-2-tert-butylamino)-3¢-chloropropiophenone · HCl) is a nonselective inhibitor of the dopamine transporter (DAT) and the norepinephrine transporter (NET) and is also an antagonist at neuronal nicotinic acetylcholine receptors (nAChRs). In animal models used commonly to screen for antidepressant activity, bupropion shows a positive response. Also using animal models, bupropion has been shown to attenuate nicotine-induced unconditioned behaviors, to share or enhance discriminative stimulus properties of nicotine and to have a complex effect on nicotine self-administration, i.e., low doses augmenting nicotine self-administration and high doses attenuating self-administration. Current studies show that bupropion facilitates the acquisition of nicotine conditioned place preference in rats, further suggesting that bupropion enhances the rewarding properties of nicotine. Bupropion has been shown to attenuate the expression of nicotine withdrawal symptoms in both animal models and human subjects. With respect to relapse, current studies show that bupropion attenuates nicotine-induced reinstatement in rats, but large individual differences are apparent. Clinically, bupropion is used as a treatment for two indications, as an antidepressant, the indication for which it was developed, and as a tobacco use cessation agent. In clinical trials, bupropion is being tested as a candidate treatment for psychostimulant drug abuse, attention-deficit hyperactivity disorder (ADHD) and obesity. Bupropion is available in three bioequivalent oral formulations, immediate release (IR), sustained release (SR), and extended release (XL). Extensive hepatic

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Section: Animal Models Of Depressionmentioning

confidence: 99%

Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent

et al. 2006

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“…Interestingly, the pharmacological potency of the two enantiomers of 1 did not differ significantly in the tetrabenazine-induced sedation model or in the inhibition of biogenic amine uptake assays. However, these tests were conducted under conditions which favour racemization of the enantiomers of 1 which may, in part, explain the lack of stereochemical specificity (Musso et al, 1993).…”

Section: Application To Steady-state Plasma Samplesmentioning

confidence: 99%

Enantiomeric Determination of the Phenylmorpholinol Metabolite of Bupropion in Human Plasma Using Coupled Achiral-Chiral Liquid Chromatography

Suckow

Zhang

Cooper

1997

Biomed. Chromatogr.

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“…As such, it is assumed that (2)-cocaine is actually S-cocaine and (1)-cocaine is R-cocaine; however, this rule is cocaine specific and may differ for other compounds. Bupropion (another reuptake inhibitor and cathinone analog) lacks stereospecificity (Musso et al, 1993). These contrasting results suggest that the contribution of each enantiomer to the observed effects of the racemate among a group of structurally related compounds may be compound and assay specific, emphasizing the need to conduct experiments with the MDPV enantiomers across multiple measures.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Effects of Abused "Bath Salt" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation

Gannon

Williamson

Suzuki

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit "bath salts" products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(1)-MDPV, and R(2)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(1)-MDPV, and R(2)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(1)-MDPV was most potent, racemic MDPV was less potent than the S(1) enantiomer, and R(2)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(1)-MDPV and racemic MDPV, but R(2)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(2)-MDPV is less potent than S(1)-MDPV and racemic MDPV. Taken together, these data suggest that the S(1)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse.

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Synthesis and evaluation of the antidepressant activity of the enantiomers of bupropion

Cited by 39 publications

References 5 publications

Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent

Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent

Enantiomeric Determination of the Phenylmorpholinol Metabolite of Bupropion in Human Plasma Using Coupled Achiral-Chiral Liquid Chromatography

Stereoselective Effects of Abused "Bath Salt" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation

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