Species variations in the N-oxidation of chlorphentermine

Caldwell, John; Köster, U.; Smith, Robert L.; Williams, R. T.

doi:10.1016/0006-2952(75)90259-2

Cited by 34 publications

(6 citation statements)

References 12 publications

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“…In 3-BMAP and 4-BMAP, there is a bromine atom on the aromatic ring at the 3-or 4-positions, respectively. Ring substitution at these positions seems to prevent aromatic hydroxylation [Bruce and Maynard, 1968;Caldwell et al, 1975]. It is therefore possible that 3-BMAP and 4-BMAP are less potent as locomotor stimulants in part because they cannot undergo para-hydroxylation to yield a behaviorally active metabolite similar to parahydroxyamphetamine.…”

Section: Discussionmentioning

confidence: 99%

Novel aminopropiophenones as potential antidepressants

Foley

Cozzi

2003

Drug Development Research

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The atypical antidepressant drug bupropion and the psychostimulant drug methcathinone are both members of a chemical class known as aminopropiophenones. Differences in the psychoactive effects of these two drugs result from small variations in their chemical structures, but the relationship between chemical structure and psychoactivity has not been characterized. To investigate how structural modifications to aminopropiophenones affect antidepressant or stimulant activity, we synthesized several analogs of bupropion and methcathinone and tested the new compounds for antidepressant-like or psychostimulant effects. The synthesized compounds are 2-(methylamino)-1-(3-bromophenyl)propan-1-one (3-BMAP), 2-(methylamino)-1-(4-bromophenyl)propan-1-one (4-BMAP), 2-(iso-propylamino)-1-phenylpropan-1-one (i-PAP), and 2-(tert-butylamino)-1-phenylpropan-1-one (t-BAP). Bupropion, methcathinone, desipramine, and the newly-synthesized aminopropiophenones were administered to rats for behavioral testing. We used the Porsolt swim test to assess antidepressant-like activity and a locomotor activity assay to test for psychostimulant effects. All of the compounds displayed antidepressantlike effects in the Porsolt swim test. Some compounds, including bupropion, increased locomotor activity at moderate-to-high doses. A halogenated analog of methcathinone, 4-BMAP, increased swim time but did not stimulate locomotor activity, even at the highest dose tested. The data indicate that phenyl ring substitution or branched alkylamines can shift the psychopharmacological profile of aminopropiophenones from stimulant activity to antidepressant-like activity. Several of the new drugs may be effective antidepressants in humans with fewer stimulant-like side effects compared to bupropion. Drug Dev. Res. 60:252-260, 2003.

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Section: Discussionmentioning

confidence: 99%

Novel aminopropiophenones as potential antidepressants

Foley

Cozzi

2003

Drug Development Research

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“…In chlorphentermine, the para position of amphetamine is blocked, and one could predict that the rat would have difficulty in metabolizing chlorphentermine, whereas the guinea pig and rabbit would attack the side chain. In fact, in the rat, chlorphentermine is slowly excreted mainly unchanged, whereas in the guinea pig and rabbit, nearly half the chlorphentermine excreted is in the form of metabolites in which the side chain NH2 group is oxidized mainly to N-hydroxychlorphetermine and its O-glucuronide (10).…”

Section: Comparative Metabolism Of Amphetaminementioning

confidence: 99%

Species variations in the pathways of drug metabolism.

Rt¹

1978

Environ Health Perspect

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“…The difference between the amounts of total N-oxidized metabolites and the added amounts of free and conjugated II was equivalent to 18% of the dose (Table 3) present in the urine. Neither p-chlorobenzoic acid, free or conjugated, nor conjugated I were excreted in the urine although the latter has been identified in the urine of animals dosed with I (Dubnick et al, 1968;Koster, Caldwell & Smith, 1974) but not that of man (Caldwell et al, 1975). CHLORPHENTERMINE IN MAN 199 metabolic products excreted in the urine under the above conditions, was 13 h.…”

Section: Calibration Curvesmentioning

confidence: 99%

The metabolism, distribution and elimination of chlorphentermine in man.

Beckett¹,

Belanger²

1977

Brit J Clinical Pharma

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I A gas-liquid chromatography procedure for the determination of chlorphentermine (I), N-hydroxychlorphentermine (II) and a,o-dimethyl-a-nitro-,-44-chlorophenyl)ethane (IV) in urine has been developed. Also methods are reported to determine conjugated II and the total N-oxidized metabolites of I, i.e. II, conjugated II, a,a-dimethyl-a-nitroso-3-(4-chlorophenyl)ethane (III) and IV in urine.2 The synthesis of ,ct-dimethyl-a-nitroso-f-(4-chlorophenyl)ethane (III) and its properties are reported. 3 The kinetics of urinary excretion of I and its metabolic products after the oral administration of I to a human subject on separate occasions have been studied. Under normal conditions of urinary pH, metabolism by N-oxidation was the main elimination route of I; acidifying the urine increased the urinary excretion of unchanged I at the expense of the N-oxidized products. 4 The importance of the N-oxidation metabolic route in the distribution of chlorphentermine (I) in man is discussed.

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Species variations in the N-oxidation of chlorphentermine

Cited by 34 publications

References 12 publications

Novel aminopropiophenones as potential antidepressants

Novel aminopropiophenones as potential antidepressants

Species variations in the pathways of drug metabolism.

The metabolism, distribution and elimination of chlorphentermine in man.

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