Possible anomalous behaviour of apomorphine in relation to other dopamine receptor agonists

Concentrations of dopamine (DA) analogues were determined in rat brain regions and serum after peripheral administration of the drugs. The time course of the concentrations of four N,N-dialkylated DA derivatives is reported in relation to the simultaneously measured effects on DA metabolism. Maximum brain concentrations were reached at about 10 min after injection, followed by a rapid elimination of the parent compounds. O-Methylation was found to be of major importance in this early disappearance. The 3-O-methyl metabolite of N,N-dipropyl-DA (DiPr-DA) was very rapidly formed and was eliminated much more slowly than the parent compound. Inhibition of O-methylation as well as subcutaneous, instead of intraperitoneal (ip), administration resulted in higher brain and serum levels of DiPr-DA. Brain concentrations of 11 DA analogues were determined 10 min after ip injection and were compared with their octanol/water (pH 7.4) partition coefficients. Within one group of compounds with a similar metabolic profile the brain concentrations and partition coefficients showed a good correlation.

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Brain and serum concentrations of dopamine analogues after peripheral administration to rats

Feenstra

Homan

Everts

et al. 1984

Naunyn-Schmiedeberg's Arch. Pharmacol.

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Possible anomalous behaviour of apomorphine in relation to other dopamine receptor agonists

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Brain and serum concentrations of dopamine analogues after peripheral administration to rats

Brain and serum concentrations of dopamine analogues after peripheral administration to rats

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