Metabolism of dopamine analogues in rat.
1. The metabolism of dopamine analogues, differing in their ring substituents and length of side chain, has been examined in rat. 2. Both benzylamines and phenethylamines were converted to their analogous acids. Where sought, the corresponding alcohols were present only in minute traces, or were undetectable. 3. Benzylamines were largely excreted as such, possibly conjugated, and this output, together with acid metabolites, accounts for most of the dose. In contrast, only a minor part of the phenethylamine dose was excreted unchanged, and much of what was given remains unaccounted for. 4. With increasing chain length the proportion of the dose found as urinary metabolites decreases markedly; long-chain (hydrophobic) amines may be sequestered in fat depots rendering them largely unavailable for metabolism. 5. beta-Oxidation of long-chain aromatic acids is observed. 6. Catechols showed evidence of O-methylation, and some O-methyl compounds were demethylated. N-methylation and N-demethylation were, at best, very minor pathways. 7. No overall pattern emerged between the position of substituents and the extent of oxidation by monoamine oxidase. No pattern at all was apparent with the benzylamines. Phenethylamines showed a trend towards a lower rate of metabolism for secondary and tertiary amines. Phenethylamines and propylamines with ortho substituents exhibited a lower rate of metabolite excretion than did their analogues.
Department of Chemical Pathology, Queen Charlotte's and Chelsea Hospital, London, UK.
B L
BL
Goodwin
C R
CR
Ruthven
M
M
Sandler
D000818:Animals; D001596:Benzylamines / Q000378:metabolism; D003641:Deamination; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D010627:Phenethylamines / Q000378:metabolism; D010648:Phenylacetates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D001596:Benzylamines; D010627:Phenethylamines; D010648:Phenylacetates; C025136:phenylacetic acid; D004298:Dopamine