Neurochemical and behavioural profiles of five dopamine analogues.
The dopaminergic actions of five hydroxylated dopamine analogues have been examined for: i) Ability to induce stereotypy, ii) Effects upon dopamine metabolism, iii) Ability to antagonise the rise in striatal dopamine caused by gammabutyrolactone. With the exception of the resorcinol derivative 2-(3,5-dihydroxyphenyl)-N,N-dipropylethylamine, all of the compounds tested exhibited dopamine-like actions, and similarities were found in the induction of stereotypy and in the reduction of dopamine metabolism. For example, 2-(3-hydroxyphenyl)-N,N-dipropylethylamine had a short duration of action as far as reducing dopamine metabolism and inducing stereotypy were concerned. On the other hand, 2-(3-hydroxyphenyl)-N-n-propyl-N-phenyl-ethyl-ethylamine (e) and also 5-hydroxy-2-(N-n-propyl-N-phenylethyl)-aminotetralin had a long duration of agonist-like effects upon both parameters, the aminotetralin derivative being the more potent of the two. Thus, in going from the simple dopamine-like structure to the aminotetralin compound there has been an increase in dopamine agonist-like activity. The differences in dopamine agonist potency of the drugs used are discussed in relation to the structure of these compounds, and are compared with the potencies or related compounds. Also, the potencies of the compounds under investigation upon presynaptic dopamine receptors (using the gammabutyrolactone model as a test system) were investigated, and the ester, 2-(3-benzoyloxyphenyl)-N-n-propyl-N-phenylethyl-ethylamine was the most potent. This ester, which is probably converted to (e) in the brain, also had a long duration of action in the stereotypy and dopamine metabolism tests. The results suggest that certain of the compounds might be useful leads for the design of dopamine agonists of possible clinical use.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015107:4-Butyrolactone; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D015102:3,4-Dihydroxyphenylacetic Acid; D015107:4-Butyrolactone; D004298:Dopamine